Ten years ago, young Integra Hellsing ascends to the head of the Hellsing Organization after the death of her father Arthur. Her jealous uncle Richard Hellsing attempts to kill her, but in doing so awakens a dormant Alucard, who proceeds to kill Richard's men. It is Integra who shoots and kills her uncle, thereby becoming the last descendant of the Hellsing bloodline. Alucard declares his allegiance to Integra and becomes her loyal servant. In present day England, Alucard is called to duty to eradicate a vampire priest and his ghouls. However, a policewoman named Seras Victoria is gravely injured in the process, and upon giving her a choice to live or die, Alucard turns her into his vampire servant. Later, on a mission to hunt down a vampire in the town of Badrick in Northern Ireland, Alucard meets and fights Father Alexander Anderson for the first time.

Alucard has a dream about his defeat at the hands of Abraham Van Helsing. While Sir Integra holds a round table conference to report her findings regarding the current wave of vampire attacks, vampire brothers Jan and Luke Valentine launch a covert sneak attack on the Hellsing compound with the help of a ghoul army outfitted with military gear and small arms. Almost all of the Hellsing soldiers are killed in the process and turned into ghouls before Alucard, Seras and Walter C. Dornez (who shows why he was once known as the "Angel of Death") are able to turn the tide. Jan reveals the name of the group responsible for the attack as Millennium. Integra hints to Walter that surviving Nazi officials could have been responsible for the attack.

In a bid to increase manpower following the devastating attack on Hellsing headquarters, Walter recruits the mercenary group known as Wild Geese and integrates them into Hellsing's security forces. Integra receives information from Enrico Maxwell, the fanatical leader of Iscariot, that confirms her suspicions of Millennium's origins. She soon deploys Alucard, Seras and Pip Bernadotte, leader of the Wild Geese, to Rio de Janeiro, Brazil to find the whereabouts of Millennium. Alucard and Seras are later attacked by BOPE units of the Brazilian military police after being declared in public as international terrorists, a ruse perpetrated by Brazilian officials in exchange for immortality promised by Millennium. After receiving orders from Sir Integra, Alucard massacres the BOPE officers and faces off against Millennium officer Tubalcain Alhambra.

As Hellsing and Iscariot hold a meeting with the Queen of the United Kingdom their conference is interrupted by a message from The Major (via live video transmission brought in by the ubiquitous Schrödinger) citing his intention to wage war on England. Meanwhile, a VTOL aircraft carrier called the Eagle gets hijacked by First Lieutenant Rip Van Winkle and a small squadron of SS soldiers from Millennium, Integra sends Alucard aboard an SR-71 to take care of the perpetrators and Rip Van Winkle in which he ruthlessly kills all of them and has Rip Van Winkle turned into one of his many familiars while the major begins to move to London to drive England into another war.

While Alucard remains trapped on the Eagle, Millennium starts attacking London. Zorin Blitz is told to head toward Hellsing HQ with a small group of soldiers, while the rest of the vampires attack London. They kill thousands of civilians and attempt to capture Integra. She manages to escape the vampire SS soldiers only after Walter sacrifices himself to hold them off; however, Walter is captured himself by The Captain. When the vampire soldiers manage to corner her, she is saved and later captured by a large group of pistol-wielding Iscariot priests, led by Alexander Anderson, Heinkel Wolfe and Yumie Takagi. After the credits, Alucard uses his powers to steer the Eagle towards London.

As the battle commences, back at the Vatican Enrico Maxwell, the head of Section XIII Iscariot is given a major promotion, and with it he begins to mobilize the Vatican's fighters. Meanwhile, in the heart of London, while Integra is busy convincing the Iscariot members to escort her home, the Hellsing Mansion is under siege by Zorin Blitz and her forces. The only line of defense against this assault are Captain Bernadotte, his Wild Geese, and Seras. As the battle rages on, they must deal with the resilient vampire Nazi forces, as well as Zorin's mysterious power of illusion that almost destroys the Geese from within. The quick thinking of Seras frees them from Zorin's grip, but the battle is not over. After an attempted stolen kiss, the group splits up, Seras in one direction and the Geese in another, but not before promising each other they'll come out of this alive. OVA 6 features a drama CD of Crossfire.

While Seras is successfully overcoming Zorin's soldiers, Bernadotte and his forces are being slaughtered. Seras comes to their rescue, and destroys most of Zorin's forces. Zorin then delves deep into Seras' memories, forcing her to relive her painful childhood, as she had to watch her parents be murdered by gangsters and her mother's corpse being raped after Seras was shot by one of the robbers. While Seras is trapped in the illusion, Zorin hacks off her arm, stabs her through the back, and cuts her eyes. Bernadotte tries to escape with the badly wounded Seras, but Zorin stabs him through the back. He kisses Seras in his agony, then tells her to bite him. Tearfully, she does so, healing most of her wounds except her left arm, which spews shadow matter. Seras destroys all of Zorin's forces, then attacks and kills Zorin. Seras then leaves the mansion and heads off to destroy the remaining vampires and ghouls in the city, as Vatican forces loom in the horizon.

The Vatican forces led by Enrico Maxwell begin to attack the remaining Millennium forces along with the surviving citizens of London. Walter, now a vampire, joins forces with the Major. Alexander Anderson is enraged because he believes Maxwell has become drunk with power and is abusing God's power. The armed priests led by Heinkel Wolfe and Yumie Takagi come close to capturing Integra, but Seras saves her. Alucard, stands atop the Eagle as it floats down the Thames, now returns to London and joins the battle encountering the two other trump cards Anderson and The Captain. Integra releases his Control Art Restriction to Level Zero allowing Alucard to summon millions of Familiars to the battle. Enrico Maxwell and Anderson realize that Alucard is in fact Count Dracula/Vlad the Impaler. Alucard's forces easily overwhelm all of the Iscariot and Millennium forces and Maxwell is killed shortly after. Alucard meets up with Integra and Seras. Anderson and Alucard fight each other but Alucard has the upper hand and the remaining priests come to aid Anderson against Alucard. Anderson uses Helena's Nail to become a monster against Alucard, setting him and his familiars ablaze.

A dying Alucard envisions his past as Vlad the Impaler, recalling how he was raped as a child by the Ottoman Sultan. He then envisions himself during his war against the Turks, stating to his knights that praying to God is pointless unless you are willing to work for your prayer, otherwise it is just begging. He is shown eventually being carried off to execution, but before being beheaded, he drinks the blood of the battlefield and becomes a vampire. He is then awoken by the pleading of Seras, who is trying in vain to help him against Priest Anderson of the Vatican. Alucard manages to rip Anderson's heart out, and crushes it, removing Helena's Nail. The priest hears the laughter of children, and says a final "Amen" before dying. Suddenly, Walter appears, crushing the remains of Anderson. Shocked at the newly vampirized Walter, Integra and Seras question him. Walter kills Yumie and replies that he now stands alone as the Angel of Death. Heinkel is shot by the Captain and badly injured, but is spared. Alucard and Walter prepare to fight, while Integra and Seras are invited aboard the Major's zeppelin to face him. As their fight goes on, Walter is growing unstable from the vampirization procedure but Walter pierces Alucard's heart with a pipe, only for the body to be revealed as a decoy. Alucard then appears from behind and punches Walter, the damage forcing his body's age to regress to the young boy from 60 years ago. Alucard fully reveals himself in the form of the girl he assumed during the war, calling Walter a child who has not changed in 60 years.

Integra and Seras battle the remnants of Millennium aboard the zeppelin until the Captain intercepts them, with Seras staying to fight while Integra proceeds onward. Outside, Alucard begins to absorb the rivers of blood from the dead, though the Major had planned on this moment to defeat him. Elsewhere Seras struggles against the Captain, who turns out to be a werewolf. Seras seems outmatched by the Captain, but is eventually aided by her familiar Bernadotte, who uses a silver tooth to slay the werewolf. Integra reaches the Major, but a shield impedes her attack, which leaves them both to witness Alucard's defeat. Schrödinger allows his body to be absorbed while the Major explains his power of omnipresence: as long as Schrödinger is self-aware, he is alive, but that the millions of lives within the rivers of blood flowing into Alucard negate his awareness/existence. This negation spreads to Alucard, which forces him to disappear. While Seras rejoins Integra, outside Walter is attacked by Heinkel, though the wounded Walter escapes into the zeppelin. Inside Seras is eventually able to pierce the shield and damage the Major. It is revealed that he is actually a cyborg, though he defends his humanity while challenging Integra. The resulting shootout kills the Major and blinds Integra in her left eye. Meanwhile Walter confronts and kills the Doctor, then passes away. Acknowledging his death, Integra orders Seras to bring them home. Thirty years later, Iscariot visits the new Hellsing headquarters but is turned away, while Heinkel as the new trump card and the new chief Makube contemplate the next Crusade. That night, Alucard reappears at the older Integra's bedside. He explains to her and Seras that the reason he was gone for so long was that the millions of lives within him were clouding his awareness. He killed them all except one, saying "I have returned here. But I am also always nowhere... The truth of it is, I am everywhere," alluding that Schrodinger is the one