Gaffigan was born in Chesterton, Indiana, and attended LaPorte La Lumiere High School. He is one of six children, plus a cat and often jokes about growing up in a large family. He is married to Jeannie Noth, with whom he has two daughters, and one son, Jack.
Gaffigan is a practicing Catholic. He attended one year at Purdue University where he was a member of Phi Gamma Delta. He graduated from Georgetown University's McDonough School of Business in 1988.