The cartoon character, best known for his love of eating, beat schoolboy wizard Harry Potter to the top slot.
People relate to Homer "because we're all secretly propelled by desires we can't admit to," creator Matt Groening told the US magazine.
Buffy the Vampire Slayer, played by Sarah Michelle Gellar, came third.
In fourth place was Tony Soprano from US drama series The Sopranos, followed by comic book villain The Joker, played by late Australian actor Heath Ledger in The Dark Knight.
Other famous characters which were included in the top 10 were Rachel from Friends, Johnny Depp's Edward Scissorhands and Anthony Hopkins' Hannibal Lecter.
Sarah Jessica Parker's Carrie Bradshaw from Sex And The City and cartoon character Spongebob Squarepants rounded out the list.