The Brain (voiced by Maurice LaMarche) looks and sounds a little like Orson Welles. In "What Ever Happened to Baby Brain", Brain actually crosses paths with Welles, who is working as a busboy in a Hollywood restaurant; they find themselves inadvertently yelling in unison, "Things will be different when I take over the world!" In "Project B.R.A.I.N." Brain's name is the acronym for the eponymous project: "Biological Recombinant Algorithmic Intelligence Nexus".[8] His tail is bent like a staircase—he often uses it to pick the lock of the cage—and his head is large and wide, housing his abnormally large brain. He is highly intelligent and develops complex plans for global domination using politics, cultural references, and his own inventions toward his goal. He seems coldly unemotional, speaking in a snarky deadpan. Nevertheless, Brain has a subtle sense of humor and has even fallen in love; with Trudie in the episode "The Third Mouse" and with Billie in "The World Can Wait".[11] Due to his stature and megalomania, Brain has been compared to Don Quixote[12] and (inaccurate) pop culture depictions of Napoleon Bonaparte.

Brain sees his inevitable rise to power as good for the world, and not mere megalomania. In Wakko's Wish, he said to Pinky "We're on our way to fame, fortune and a world that's a better place for all." Many of the Brain's plots had the endgame of winning over the people's hearts and having them make him their ruler. However, his motives are not pure. In one episode, Brain finds himself hypnotized by a psychologist he had planned to manipulate for one of his schemes, who turns out to be none other than Sigmund Freud. There Brain reveals that he originally lived with his parents in a tin can at the base of a tree in a large field. When he was young, ACME researchers captured Brain and took him from his home, and the last he saw of it was a picture of the world on the side of the can. Dr. Freud speculates that Brain's hunger to take over the world is misplaced, and that all he really wants is to go back home to his parents.[14] According to the creators, Brain wants to take over the world not for the sake of being a dictator, like his rival Snowball, but because he believes that he could do a much better job of it than the people currently in charge. Brain has even helped save the world by doing everything in his power to prevent Snowball's evil schemes, knowing that a world under Snowball's rule would be the worst case scenario.

Similarity to Orson Welles

Brain's similarity to Orson Welles was made explicit in the episode Yes, Always, which was based upon an outtake from one of Orson's Television commercials, colloquially known as "Frozen Peas," in which he ranted about the poor quality of the script. This cartoon was described by screenwriter Peter Hastings as "a $250,000 in-joke:" Maurice used excerpts from it as sound check material, and Peter took it to its logical decision. Strengthening the Orson Welles connection was an episode in which Brain took on the mind-clouding powers of a radio character called "The Fog:" a parody of The Shadow, a popular radio character for which Orson once provided the voice. Other episodes alluding to Orson Welles include an episode entitled "The Third Mouse" (a parody of The Third Man), in which Orson? appeared, and an episode in which Brain, inspired by Orson's infamous War Of The Worlds radio broadcast and the hysteria it provoked, stages an alien invasion on television, believing that this will cause humanity to turn itself over to his rule.

Why does he always fail to take over the world?

All of Brain's attempts to take over the world fail. There is more than one reason for this. Sometimes, he realizes a flaw in his plan that he should have realized earlier, such as in “Opportunity Knox”, where he forgot that gold is extremely heavy. Other times, Pinky screws things up, such as in “Brain Meets Brawn”, when he apologized to Brain after making a mistake. On other occasions, it's neither one of them, but something else that causes him to fail.

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