Berninger is a 1989 graduate of St. Xavier High School in Cincinnati where he played trumpet for the high school's band. He went on to study graphic design at the University of Cincinnati, where he met fellow band member, Scott Devendorf in 1991 and they became best friends. Berninger quit a career in advertising in his thirties to start the National. He told The Telegraph: “I was doing well [in advertising]. But, once I entertained the thought that maybe I wouldn’t ever have to go and sit in conference rooms with Mastercard to discuss web ads again, I couldn’t shake it.”
Matt is married to Carin Besser, a one-time fiction editor for The New Yorker, who has often contributed to the band's songwriting ("Brainy" and "Ada" from the album Boxer) and backup vocals. Together with Hope Hall and Andreas Burgess, Carin also helped direct the music video for "Bloodbuzz Ohio". They have a daughter, Isla. Matt has stated that the song "Afraid of Everyone" was influenced by his anxiety about being a new father.