Agent Venom (Flash Thompson) was attacked by the FBI using a specialized anti-symbiote suit of armor. Agent Venom was struck by a beam that separated him from the symbiote, which relapsed into its murderous state and abandoned him. Falling into depression with the loss of his friend and what had made him a superhero, Flash was able to renew his determination to rescue the symbiote from whoever had taken it.
After learning that Mania had her symbiote stolen, Flash assumed the culprit was the one responsible for separating him from the Venom symbiote. Using the traces of the Venom symbiote inside his body as a compass, Flash tracked it to Alchemax Tower, where he discovered it had re-bonded to Eddie Brock. Flash confronted Brock and attempted to have the symbiote return to him. While the symbiote was struggling to decide which host to go to and latched to both men at the same time, Spider-Man appeared on the scene. He overturned a vat of artificial Anti-Venom serum developed by Alchemax on Flash and Eddie in an attempt to kill the symbiote. Instead of killing the symbiote, the serum turned the portion of it bonded with Flash into a new Anti-Venom, which transformed Flash into a color-inverted version of his Agent Venom form. Flash was able to use the Anti-Venom symbiote to completely remove the Venom symbiote from Eddie, but couldn't bond with it himself. Leaving the symbiote at Bobbi Morse's apartment for safekeeping, Anti-Venom and Spider-Man set out to track down the Mania symbiote and traced it to Black Cat's hideout, where they discovered Felicia's gang had been infected with the symbiote by its new host, Maniac.
Spider-Man and Anti-Venom were defeated, and Maniac tried to burn Flash and his symbiote alive. They were rescued by Andi, who was using the powers derived from the Hell-Mark to keep fighting without her symbiote. Anti-Venom and Andi then tracked down Spider-Man, who had fallen under Maniac's control, and tried to free him. They were assisted by Black Cat and Eddie Brock, who had merged back with the Venom symbiote after it escaped Morse's apartment. The heroes then followed Maniac to a gathering of the five biggest crime families in the world, where he had used his symbiote to take control of all attendees. Using weaponry coated in Alchemax's Anti-Venom serum and Flash's own symbiote, the heroes freed those under Maniac's control, prompting him to have the remains of the symbiote return to him to make him stronger. Maniac initially overpowered the heroes until Black Cat noticed those freed from his control by Anti-Venom developed immunity to him. Spider-Man had Flash's symbiote absorb a sample of his blood to absorb its "Anti-Maniac" properties, giving Flash the boost necessary to strike Maniac down and neutralize him. With Maniac defeated, Flash called his contacts from the government to take him away. Before they disbanded their alliance, Anti-Venom gave Brock his blessing to keep the symbiote, arguing he displayed his heroism when fighting Maniac.
When word got out that the Poisons were using symbiotes to attack superheroes, Alchemax called in favor of Flash to use his anti-symbiote properties to help out. Flash agreed initially, despite Venom's angry protests and concern for the victimized symbiotes, but no alternative could be found. Agent Anti-Venom then accompanied Venom and Spider-Man to aid several superheroes in fighting off the Poisons and attempted to capture one of the bound Poisons to strip them of their symbiote and interrogate them. However, when Agent Anti-Venom tried to rid Poison Punisher of his symbiote, he was horrified when his Anti-Venom powers caused the Poison to shriek in pain and collapse into a puddle, with no sign of the human host inside.
Despite his new concerns about using his powers against the Poisons and harming any innocent humans within, Agent Anti-Venom was assigned to one of two teams to attack Thanos' Ship in Earth Orbit. After fighting off an assault on Alchemax by a group of Poisons, Agent Anti-Venom boarded a Quinjet with his team and set off to the Poisons' ship, only for the Quinjet to be destroyed mid-air by Poison Thanos. Agent Anti-Venom, having survived the crash and having no qualms about using his powers on one such as Thanos, leaped into battle against the Poison, shrugging off attempts by Poisons to assimilate him, but was quickly struck down by Poison Thanos' power. As Flash's companions were also laid low by the former Mad Titan, Kid Kaiju summoned his monsters to attack.
Unfortunately, one of Kid Kaiju's monsters, Scragg, was forcibly bonded to a symbiote during the battle and consumed by a Poison, creating Poison Scragg. Recognizing the threat such a beast posed to New York, Agent Anti-Venom reluctantly used his powers to destabilize Poison Scragg and allow him to be mercy-killed by Slizzik. Agent Anti-Venom then set about healing his injured companions and witnessed the systematic self-destruction of the Poisons after the death of their Queen.
As Agent Anti-Venom, Flash experienced unprecedented popularity surpassing that of Spider-Man. However, he was blackmailed by Liz Allan - who had seen and destroyed footage of Flash bonding to the altered symbiote - into providing extra security at her company's new off-site testing facility, where she was going to do a demonstration on the potency of tritium. Flash reluctantly agreed, worried she would expose him if he refused; and when the Goblin King and several of his thugs attacked to steal the tritium Agent Anti-Venom teamed up with Spider-Man to try to stop them - though as a result of Flash leaving to heal one of the guards the Goblin King was able to make off with a small amount. Liz blackmailed Flash once more into helping her track it down, and he arrived at an old nightclub once used as a hideout by the Green Goblin. Inside, he discovered Urich's mutilated corpse and a tied-up J. Jonah Jameson, who informed him that Osborn had not only become the Green Goblin again but had bonded to the Carnage symbiote.
Contacted by Spider-Man, Agent Anti-Venom was asked to watch over Jameson - who used the distraction to sneak away. When the Red Goblin mortally wounded the Human Torch, Clash, Silk, and Ultimate Spider-Man; Flash chose to sacrifice his opportunity to defeat Osborn using the Anti-Venom symbiote's cleansing properties to heal Spider-Man's friends and was badly mauled as a result of overusing its healing powers. Using the last of his energy to heal Spider-Man's leg, Flash was taken to the hospital, where he learned that Spider-Man was Peter Parker from a delirious Cindy Moon, and used the last of his power to save Spider-Man's friends and loved ones from Carnage. Arriving to confront the Red Goblin alongside Spider-Man - who had bonded to the Venom symbiote - Flash tried to use the last of the Anti-Venom symbiote to purge Osborn of the Carnage symbiote. In retaliation to Flash ruining his plans, Osborn mortally wounded Flash with his Sparkle Blast gauntlets before being punched across the city by a berserk Venomized Spider-Man. Flash managed to calm Venom down and asked Peter to not give in to rage lest he corrupts the symbiote, refusing to rebond to it out of concern that the remaining Anti-Venom in his body would kill it or he would die before it could heal him, killing it and depriving Spider-Man of the advantage it conferred. Flash died of his injuries and was later given a military funeral with full honors.
