Blade starts when a creature assaults a pregnant woman and causes her to labor. The woman is taken into the hospital where she is operated on to give birth to her baby. Unfortunately, the woman dies after she delivers her child.
Years pass and a new scene unfolds. In a club run by vampires, the vampire hunter Eric “Blade” Brooks comes just in time to save a man from being feasted on by vampires. Blade kills the vampires except for one whom he sets on fire before fleeing the scene. The burnt vampire, Quinn, survives and starts killing as soon as he wakes in the hospital. Blade arrives again and saves Karen who has been bitten by Quinn. Blade’s colleagues inject Karen with something that can prevent from transforming into a vampire. Karen learns from Blade and his group everything about vampires and that she must immediately leave town to avoid the vampires.
On the side of the vampires, the elders and a young vampire named Deacon Frost are arguing whether vampires should openly dominate humans or just manipulate them from the shadows. The elders believe that vampires should not be exposed to humans while Frost believes otherwise. Because his suggestions are disregarded, Frost murders the head vampire and hostages the remaining elders.
In Karen’s apartment, a familiar tries to attack her. Blade defeats him and pries out some information from him. Blade and Karen arrives in an archive and learn about a prophecy about La Magra or the Blood God. After some time, vampires come in to attack them. Fortunately, one of Blade’s colleagues, Whistler comes to their aid. After the altercation, Karen learns that Blade is a half-vampire and must always injects himself with a serum to suppress his blood thirst.
Blade’s condition prompts Karen to search for a cure. She succeeds in formulating a serum that reverse the transformation of turned vampires. However, the serum fails to cure Blade. Meanwhile, Frost tries to persuade Blade to join him. Blade declines and leaves. When he comes back to their headquarters, he finds out that Karen is missing, obviously taken hostage by vampires.
Blade comes after the vampires and shockingly encounters his mother in Frost’s place. Blade learns that Frost was the one who previously attack his mother and the one who caused him to be a half-vampire. Blade gets caught and he and Karen are brought to the Temple of Eternal Night. Blade’s blood is drained while Karen is placed in a pit. Karen manages to escape and rescue Blade by feeding him her blood. Meanwhile, Frost uses Blade’s blood and the elder’s souls to acquire their powers. Blade arrives and battles the newly empowered Frost. Blade kills him by injecting him with Karen’s serum.
The movie ends with Karen hinting that she should go and find a cure for Blade. However, Blade just advises her to work on her current serum.