It’s late at night when a pregnant woman named Vanessa is brought to the hospital with a hideous wound. The doctors say some kind of wild animal did it and try to keep her alive, only for Vanessa to start giving birth. After an arduous process, a baby boy is born and taken away while Vanessa dies.
Many years later, a seductive woman brings a naive man to a giant fridge, only to surprise him with a hidden entrance to an exclusive nightclub. They join the dancing crowd but soon the man realizes something is weird about this club. Suddenly a few drops of blood fall on his face and when he looks up, he finds the sprinkler system pouring down blood all over the place because all of the club's patrons turn out to be vampires.
The guy tries to escape by crawling on the floor, but he freezes when he sees the clean feet of a guy that makes the party instantly stop. His name is Blade, but the vampires call him “Daywalker”. He coolly enters the main dance floor and immediately begins a savage slaughter of the creatures, using a combination of martial arts and firearms to pick them off without mercy.
His weapons are custom-made with silver on the bullets and the blades, which the vampires are weak to. After fighting his way through numerous creatures, Blade is surrounded by the club’s guards led by Quinn. Another fierce battle begins, and this time Blade uses his sword and his blades to kill a bunch of vampires at the same time.
Next he goes after Quinn, nailing him to the wall with stakes and setting him alight while sending his regards to Frost. At that moment sirens announce the arrival of the police, so Blade runs away, leaving a burnt Quinn and a very confused human as the only surviving inhabitants. Assuming he’s dead, the police take Quinn's crisp remains to the hospital for examination.
The doctor chosen for this is Karen, who immediately sees there’s something weird about the blood exam and notices the overgrown fangs. During the examination, Quinn shockingly returns to life and feeds on both Karen and her co-worker. However Blade enters the morgue, having already expected this.
He attacks the revived vampire, but Quinn jumps out of the building, landing inside an ambulance before running away. On his way out, Blade sees a bleeding Karen lying on the floor, begging for help. Because the doctor reminds him of his mother, Blade picks Karen up and brings her with him while he jumps to another roof, dodging the bullets from the incoming cops.
Blade shoots a few bullets back and helps Karen with her dislocated arm before they run away. By the time they make it to Blade’s hideout, Karen is unconscious, and Blade’s friend Whistler injects her with a garlic serum to fight off the transformation. If she becomes a vampire, Whistler reminds Blade he must kill her.
Meanwhile in the meeting room of The House of Erebus, the vampire Shadow Council is holding a meeting. Elder Drgonetti discusses Blade's recent intensified attacks and scolds a young vampire named Frost for his recklessness in running these clubs. It’s then revealed that most vampires believe that they should more or less co-exist with the humans while maintaining a powerful secret organization like the mafia, while renegades such as Frost believe they should rule them outright.
It is also established that there is some stigma from "pure-blood" vampires, meaning those who are born vampires towards those born human and later turned into vampires. The whole council is pure-blood, but Frost isn’t, yet he swears he’ll destroy their old ways one day. The next morning, Blade stops by a friend’s shop to get more garlic serum, explaining he’s becoming resistant to it.
His friend unfortunately can’t do much and hugs him as he reminds him to be careful. Later Karen wakes up in a strange room and is shocked to see a wall full of weapons, including a sword with a trick handle. When she comes out, she notices Whistler injecting Blade with a special serum, which makes his whole body shake.
The duo quickly sees her, and she tries to run away. However Whistler and Blade immediately block her path and assure her they’re allies. Whistler is Blade’s mentor and weapons technician, together they fight against all vampire-kind with silver bullets, UV lights, and garlic.
They can’t go to the police with this because the vampires have bought them off. Now they want her to leave, but first Whistler gives Karen a weapon known as the vampire menace so she can protect herself from the vampires that will surely come after her for knowing her secret. Meanwhile Drgonetti visits Frost to scold him for wasting time and resources researching ancient vampire legends that are probably rubbish, slapping him for it.
However Frost remains unbothered. When she arrives at her building, Karen becomes suspicious of anyone she sees, especially people with weird tattoos on their necks. She finds officer Krieger waiting in her apartment, and at first he pretends he’s here because she left the hospital without leaving a statement.
But suddenly he attacks her as he reveals he is a familiar - a human being who serves vampires and after years of service might get rewarded by being turned into a vampire. Blade suddenly shows up, knowing this would happen because he’s been using Karen as bait. He beats the cop up and shows Karen the tattoo on the officer’s neck before announcing they’ll be using him to track down Frost.
Then they check Krieger’s car and find the truck full of blood bags, so Blade takes out his gun to demand an explanation. Karen stops him before starting chaos in the city, and Kriege gets to run away. Blade decides to wait in a car outside for Krieger to appear again and Karen announces she’s staying with him because she wants to find a cure.
When night falls, Krieger comes to pick up his car, and Blade immediately begins chasing him through the city. Eventually they make it to a nightclub managed by vampires, and when they try to get inside, a guard intends to stop them, but Blade simply beats him up. Inside the club, Blade beats up more guards until Krieger tells him about a hidden entrance in the fridge that takes him to a secret archive.
After sending Krieger away with a message for Frost, Blade and Karen check the place and come across a disgusting vampire known as Pearl, who is in charge of the vampires’ files and systems. Meanwhile Frost manages to finish the translation of the ancient texts. Krieger arrives to warn him about Blade, but Frost kills him and shares him with his girlfriend.
Then he orders Quinn to capture Blade alive. Back to Pearl, at first he doesn’t want to cooperate, but then Karen begins burning him with a UV light and Pearl quickly begins spilling everything: Frost is planning to summon a blood god named La Magra. Blade steals a hard drive with the information, and Karen finishes killing Pearl with the light.
Then Blade uses a special explosive spray to blow up a door, behind which they find the ancient vampire bible. Suddenly Blade hears a noise and finds a scared little girl, but when he tries to help her, she reveals herself to be a vampire and attacks him. Quinn arrives with more guards and another fight starts during which Blade gets tied to a column, and Quinn takes the chance to stab him in revenge.
One of the vampires grabs Blade’s sword, only to lose his hand to the trap in the handle. At that moment Blade reveals he’s been wearing an earpiece in case he needed help and the wall nearby explodes, revealing Whistler. After exchanging a few more shots and punchings, Blade, Whistler, and Karen run down a tunnel right before a bomb Whistler left behind explodes.
The tunnel takes them to the subway rails, and while the train passes by, Quinn jumps on Blade to start another fight. While Whistler escapes through a sewer hole, Blade pushes Quinn against the train to make him lose half his face and a hand. Karen hands him his sword back, but this only scares Quinn away.
There are more vampires coming, so Blade grabs Karen and they escape by jumping on the train. Inside, Blade injects himself with a blood serum, and Karen begins suspecting he’s a vampire. When they make it to the hideout, Whistler explains to Karen that Blade’s mother had been bitten while she was pregnant and died after childbirth.
He had been a lost kid on the streets when Whistler found him and almost killed him, but he realized he wasn’t an actual vampire and decided to adopt him. Blade is half vampire half human, which allows him to have certain abilities like strength and regeneration but he can still walk under the sun. The serum he takes prevents him from developing a need for drinking blood.
Meanwhile Frost and his group cover themselves with sunscreen and helmets to bring Drgonetti to a sunrise, taking his fangs before letting the sun kill him instantly. Afterward Frost presents the fangs to the rest of the Shadow Council and asks for twelve "volunteers”. In the morning, Karen decides to take Whistler’s research to work on a permanent cure with Blade’s serum as a base, and her first result makes vampire blood explode.
After Karen takes a sample of his blood, Blade leaves to buy more ingredients for his serum, and Whistler checks on Karen’s wounds, saying she only has one day left. While he’s downtown, Blade finds Frost waiting for him while wearing sunscreen. The vampire is holding a little kid as a shield so Blade won’t attack him and offers a truce, but Blade knows Frost wants to bring the blood god back and is against it.
He pulls out his gun and shoots, but Frost throws the girl into traffic and runs away. Blade has no choice but to save the girl first, losing his prey. At the hideout, Karen manages to make a proper curing serum that she immediately injects herself with.
At that moment Frost and his men arrive and they beat up Whistler before leaving with a kidnapped Karen. When Blade returns, he is devastated to find Whistler’s dying body. Whistler tells him he looked at the hard drive and explains Frost’s plans, saying the ritual needs the blood of a Daywalker like Blade.
He also mentions he doesn’t want to be a vampire, so Blade respects his wishes and leaves him with a gun in order to end things for himself. Afterward Blade finds a taunting video from Frost, asking him to come find him and giving him the address. Stricken with grief, Blade arms himself up with silver and the new serum before leaving to find Frost.
Moments later, Blade breaks into Frost’s headquarters using a bike. On the first floor, he shoots every guard that dares get in his way without even breaking a sweat. On the next one, he fights hand-to-hand with two vampires expert in martial arts, but after exchanging a few hits, Blade injects them with the serum and makes them explode.
When he finally makes it to Frost's room, Blade finds a shocking surprise: Vanessa is still alive, she became a vampire shortly after giving birth. In fact it had been Frost who bit her, and now she’s his mistress. This distraction allows Frost and his guard to catch him from behind and beat him to submission.
Afterward, Blade and Karen are taken to the Temple of Eternal Night, and Blade can’t defend himself because his body is weak from thirst. Frost reveals he’s stolen the vials with the serum and throws them to the bottom of the pit before he sends Blade away to his spot to start the ritual. Karen is pushed into a hole where she finds his coworker in an almost zombie-like state because of his thirst.
There also are a bunch of bones on the floor, so Karen uses one to beat the vampire up before starting to climb out of the hole. Meanwhile Blade is tied to a special contraption for the ritual, and Vanessa gets inappropriately close to him, saying that he needs to accept she isn’t the mother he remembers. Then the contraption is closed and begins to extract Blade’s blood.
Upstairs, Frost lines the council members around the temple, and when one of them tries to resist, Frost’s girlfriend kills him. Blade’s blood begins falling on all of them and on Frost at the center, and when lightning hits the temple, it kills the entire council and passes their powers to Frost, making him the ultimate vampire god. Back to Karen, he finds Blade and frees him from the contraption, but he’s obviously too weak to survive.
Karen removes her bandage and convinces him to drink her blood, which instantly heals him and leaves him in a berserk state. At that moment Vanessa arrives and Blade immediately begins fighting her, ignoring her when she tries to sweet talk him into loving his dear mom and killing her. Afterward Blade rushes upstairs, and when Quinn tries to stop him, Blade destroys him in seconds.
Feeling powerful thanks to having drunk real blood instead of the serum, Blade begins fighting all the guards with vicious fury, not needing any weapons to kill them in a matter of seconds. Karen goes after Frost’s girlfriend, missing a few shots but remembering to use the vampire menace at the last second to get rid of her. After recovering his sword, Blade fights Frost in a furious sword battle.
Blade manages to cut Frost into many pieces, but Frost’s new powers allow him to instantly put himself back together. They begin exchanging hits again, but Frost is simply too strong and stabbing him does nothing. At that moment Blade notices the serum that fell earlier and throws his sword to retrieve them.
Then he injects Frost with all of them at the same time, causing him to explode. In the end, Blade and Karen escape the temple, and Karen offers Blade her cure. Blade refuses, because "curing" him of his need for blood would also remove his Daywalker powers and he would be unable to hunt vampires, but he wants to keep protecting the city.
Sometime later, Blade appears in Moscow, ready to kill a vampire that is about to attack a woman.
