Andrew Pepoy studied at the Loyola University Chicago, while publishing his first comic artwork in fanzine. He has worked as an inker on several titles by Marvel, DC and other publishers since the 1990s, including 'Superman', 'Spider-Man', 'Batman', 'The X-Men', 'Fables', 'Scooby Doo', 'Sonic the Hedgehog', 'Godzilla', 'Star Wars', 'G.I. Joe' and 'Wallace & Gromit'. He pencilled some issues of 'FemForce' for AC, and had his own series, called 'The Adventures of Simone & Ajax' in Mythography by Bardic Press.
In June 2000, Pepoy and writer Jay Meaders succeeded Leonard Starr on the classic 'Little Orphan Annie' newspaper strip, now simply called 'Annie', for Tribune Media Services. Pepoy was replaced by Alan Kupperberg in the following year. He has worked extensively for Archie Comics since 2006. He drew the revived 'Katy Keene' feature for 'Archie & Friends' in 2006-2007, and he has provided inks to several other Archie-related titles. He has also inked many 'Simpsons' and 'Futurama' stories for Bongo Comics, as well as the graphic novel series 'Lanfeust Odyssey' and 'Alunys' for Soleil in France. Andrew Pepoy won the Eisner Award in 2009.