Justice League Unlimited

In the first season of Justice League Unlimited, Luthor announces he is running for President of the United States; this is later revealed to be a ruse to enrage Superman. In reality, Luthor is financially backing Project Cadmus, a shadow government organization dedicated to eradicating the League if they ever turn on Earth's population. Luthor uses the project to gain access to the technology necessary to build a duplicate of A.M.A.Z.O., intending to transfer his mind into the android body and gain immortality. He is thwarted by Amanda Waller and the seven founding members of the Justice League. At this point, it is revealed that Brainiac has been hiding within Luthor ever since the events of the Superman: The Animated Series episode "Ghost in the Machine", the blast he hit Luthor with having delivered a nanotech payload with a copy of his program. The two escape the League, and Luthor convinces Brainiac to merge with him into a single being using alien nanotechnology. Brainiac is thus reborn with a new purpose: absorb all information in the universe and then remake it. The combined being is defeated by the Flash in the first and only demonstration of the Speed Force in the series.

In the following season, Luthor continually speaks to a hallucination of Brainiac, giving him a sort of multiple personality disorder; it is never made clear if the hallucination is actually Brainiac or merely a figment of Luthor's imagination. Luthor is obsessed with rebuilding Brainiac and regaining his lost "godhood". He joins the Secret Society, led by Gorilla Grodd, in order to obtain a piece of Brainiac in Grodd's possession. Later, using the failure of Gorilla Grodd's plan to turn all humans into apes, Lex usurps and imprisons him, then assumes Grodd's place as leader.

After taking over as leader of the Secret Society, Luthor returns to trying to resurrect Brainiac. Using the power of the Secret Society headquarters, Luthor tries to bring the fragment of Brainiac back online. Eventually, with the help of Tala, Luthor tracks down the remains of Brainiac's base and reconfigures the Secret Society headquarters into a starship to reach it. During the journey, Tala frees Grodd, who mounts an insurrection against Luthor with his fellow Secret Society members. Luthor manages to turn Grodd's own telepathy against him, then forces Grodd to space himself, apparently killing him.

The Secret Society, back under Luthor's power, returns to their task of resurrecting Brainiac. Luthor hooks Tala up to a machine to gather Brainiac's essence from the remains of his base, knowing fully well that this will kill Tala. Before Luthor begins the process, Metron warns him that he may unleash something that will affect all of time. Luthor ignores the warning and proceeds, and as a result ends up mistakenly resurrecting Darkseid, fused with Brainiac, (although the DVD commentary suggests that Tala deliberately did this as her final act of revenge against Luthor), who immediately unleashes his wrath on on the Secret Society before heading to Earth. The Society survives thanks to a forcefield generated by Sinestro and Star Sapphire.

As a result of the attempt, Luthor can no longer hear Brainiac's voice. The remnants of the Secret Society, under Luthor, go to the Justice League Watchtower to warn the superheroes of the threat. Complaisant to Superman's distrust to him, Luthor made it clear that he cares less about saving the world and more about revenge on Darkseid for robbing him of his quest for power. They both agree that it will be "back to business as usual" and so made a temporary alliance in the defense of the planet. After With the aid of the New God Metron, Luthor manages to acquire the Anti-Life Equation long sought by Darkseid, and uses it on the lord of Apokolips, apparently sacrificing his own life in the process. Batman and the Flash, however, suspect Darkseid and Luthor will most likely meet them again. By the time of Batman Beyond, they have not been seen or heard from, implying that Luthor and Darkseid are indeed dead.