DeFilippo was born in 1978 in Youngstown, Ohio. His father Gene DeFilippo was then offensive coordinator for the Youngstown State University football team, a position he would hold until 1979. In 1980, the DeFilippo family moved to Nashville, as Gene became offensive backfield coach at Vanderbilt. John later spent his childhood in Spartanburg, South Carolina from 1984 to 1987 as his father was athletic director at the University of South Carolina-Spartanburg, then in Lexington, Kentucky from 1987 to 1993, when his father was associate athletic director at the University of Kentucky. In 1993, Gene DeFilippo became athletic director at Villanova University in Philadelphia. John DeFilippo enrolled at nearby Radnor High School in tenth grade and lived in a hotel with his father, from the summer to the early part of the school year. DeFilippo played quarterback on the Radnor football team. In his first start as a varsity football player, DeFilippo led Radnor to two touchdowns in the last 6:30 of Radnor's 16-14 victory over Penncrest High School. The winning score occurred when Bumper Howard fumbled into the end zone as he was being tackled, and Michael Cutler leaped onto the ball in the end zone for the crucial TD. This win ended a 34-game losing streak for Radnor but would end up Radnor's only win of the season. As a junior in 1994, DeFilippo passed for over 1,200 yards and 10 touchdowns, and Radnor finished with a 2-9 record. DeFilippo graduated from Radnor in 1996 and attended James Madison University. DeFilippo played at quarterback for the James Madison Dukes under head coachAlex Wood from 1996 to 1998 then Mickey Matthews in 1999. As a senior in 1999, DeFilippo played in 11 games as a backup and completed 8 of 18 passes for 90 yards. JMU finished the season 8–4, with the Atlantic 10 regular-season title and a berth in the Division I-AA playoffs. While a student at JMU, DeFilippo spent two summers doing NFL internships, in 1997 with the Carolina Panthers and 1998 with the Indianapolis Colts. DeFilippo graduated from JMU in 2000 with a bachelor's degree in speech communications with a concentration in public relations.
Coaching career
Early career
DeFilippo became quarterbacks coach at Fordham in 2000 upon graduating from James Madison. The following year, DeFilippo enrolled at the University of Notre Dame to be a graduate assistant for the Notre Dame Fighting Irish. 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. From 2003 to 2004, DeFilippo was again quarterbacks coach at a Division I-AA program in New York City, Columbia, under Bob Shoop. He then 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. In 2007, DeFilippo joined Lane Kiffin's staff on the Oakland Raiders as quarterbacks coach and remained on staff in 2008 when Tom Cable replaced Kiffin during the season. DeFilippo became quarterbacks coach for the New York Jets under Rex Ryan in 2009. The Jets that year finished 9-7 and in the playoffs, defeated the Cincinnati Bengals and San Diego Chargers to make their first trip to the AFC Championship Game in 11 years, before losing to their former division rival Indianapolis Colts 17-30. DeFilippo also coached rookie quarterback Mark Sanchez, whom in 2009, became only the second rookie quarterback in NFL history to win multiple playoff games. DeFilippo returned to the college ranks in 2010 as quarterbacks coach at San Jose State under Mike MacIntyre. In 2011, DeFilippo also became offensive coordinator for San Jose State, in a season where San Jose State rose 32 places in national offensive rankings and improved to 5–7 from 1–12 the previous season.
Oakland Raiders (second stint)
In 2012, DeFilippo returned to the Oakland Raiders as quarterbacks coach, first under Dennis Allen, and then Tony Sparano.
Cleveland Browns
On January 21, 2015, DeFilippo was hired as the Cleveland Browns' new offensive coordinator. However, after only one season, DeFilippo was let go after head coach Mike Pettine was fired.
Philadelphia Eagles
On January 21, 2016, DeFilippo was hired as the quarterbacks coach of the Philadelphia Eagles. In his second season as quarterbacks coach, DeFilippo and the Eagles made their first Super Bowl in 13 years, where in a rematch of Super Bowl XXXIX, the Eagles defeated the New England Patriots 41–33 to win their first Super Bowl in franchise history.
Minnesota Vikings
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 Game a month earlier. DeFilippo was fired after the Vikings lost 21–7 to the Seattle Seahawks on Monday Night Football in week 14.
Jacksonville Jaguars
On January 13, 2020, DeFilippo was fired by the Jacksonville Jaguars after only one season as the offensive coordinator.
Chicago Bears
On January 16, 2020, DeFilippo was hired by the Chicago Bears to be their quarterbacks coach on Matt Nagy's staff. DeFilippo had interviewed for the Bears' head coaching position in 2018, but lost out to Nagy.
