[1] Keeler studied applied mathematics at Harvard University, graduating summa cum laude in 1983.

[4] Keeler soon left Bell Labs to write for David Letterman and subsequently for various sitcoms, including several episodes of Wings, The Simpsons, Futurama, and The Critic, as well as the short-lived Fox claymation show The PJs.

For The Simpsons, Keeler has written such episodes as "A Star Is Burns" (which series creator Matt Groening refused to be credited for, as he was opposed to the idea of The Simpsons crossing over with The Critic) and "The Principal and the Pauper" (which many fans – including Groening and voice actor Harry Shearer – disliked due to the massive changes in Principal Skinner's backstory).

He also wrote the direct-to-DVD Futurama movies Bender's Big Score and Into the Wild Green Yonder.

[8][9] His Futurama episode "Time Keeps on Slippin'" was partly inspired by the Harry Stephen Keeler story "Strange Romance" from the novel Y. Cheung, Business Detective.