He played college football as a quarterback at James Madison University, and has served as offensive coordinator for the Cleveland Browns, Minnesota Vikings, and Jacksonville Jaguars.

His father, Gene DeFilippo, was then offensive coordinator for the Youngstown State Penguins football team, a position he held until 1979.

DeFilippo played at quarterback for the James Madison Dukes under head coach Alex Wood from 1996 to 1998 then Mickey Matthews in 1999.

[10][11] In the 2001 season, DeFilippo helped coach wide receivers and tight ends on Bob Davie's staff, then in 2002 worked with quarterbacks under Tyrone Willingham.

[9] From 2003 to 2004, DeFilippo was again quarterbacks coach at a Division I-AA program in New York City, Columbia, under Bob Shoop.

[12] He moved up to the NFL in 2005 as offensive quality control coach for the New York Giants under Tom Coughlin and held that position until 2006.

[16] DeFilippo returned to the college ranks in 2010 as quarterbacks coach at San Jose State under Mike MacIntyre.

[22][23] Four days after winning Super Bowl LII, DeFilippo was hired as offensive coordinator of the Minnesota Vikings, the same team his Eagles defeated in the NFC Championship a month earlier.

After the USFL and the XFL merged to create the United Football League, DeFilippo was named the Head Coach of the Memphis Showboats on January 1, 2024.