His most notable writing credits include work on The Defenders during the late 1970s and early 1980s. As the artist on The Spectacular Spider-Man, Hannigan co-created the characters Cloak and Dagger. He pencilled the covers on Batman in a lengthy run that spanned the majority of 1983-1985 (with Don Newton providing the interior art). He both wrote and illustrated the three-issue prestige format series Skull & Bones for DC Comics in 1992.

Hannigan was also the artist on DC Comics's first ongoing Green Arrow comic book beginning in 1987. Written by Mike Grell, creator of Jon Sable, Freelance, the series continued in the serious, realistic direction Grell had begun in his limited series, The Longbow Hunters, where in the Green Arrow sheds such of his trick-arrows as the classic boxing glove arrow, dons a Robin Hood-like costume, and lives in a Seattle flower shop with Dinah Lance, the Black Canary.

Hannigan was responsible for redesigning the character of Brainiac into his chromed, more robotic form.

Hannigan and his wife Heidi are the parents of Jean Anne, born in 1989.

In January 2010, Marvel Comics and The Hero Initiative published "Ed Hannigan: Covered" a fundraising effort to assist with Hannigan's medical expenses due to multiple sclerosis.