Cutcliffe was born and raised in Birmingham, Alabama, which played a formative role in his development as a football coach. He has two brothers (Charles "Paige" Cutcliffe, and Raymond Eugene "JR." Cutcliffe) and three sisters (Mary Marlyn Cutcliffe Sullivan, Margart Lynn Cutcliffe, and Elizabeth "Buff" Cutcliffe Easterly.) Cutcliffe attended Banks High School in Birmingham where he played football. He attended the University of Alabama, where he worked as an assistant director of the athletic dormitory.
In 1976, he took a job at Banks High School where he served as an assistant and later as the head coach. In 1982, he was hired as a part-time coach at the University of Tennessee. A year later, he was promoted to full-time status as the tight ends and assistant offensive line coach. By 1990, Cutcliffe was coaching the position he is now well known for, quarterback. Cutcliffe was promoted to offensive coordinator in 1993. As coordinator, Cutcliffe helped lead the Vols to two Southeastern Conference championships and a national championship. He also helped groom Heath Shuler and future Super Bowl MVP Peyton Manning, serving as their position coach.
On December 2, 1998, Cutcliffe was hired as the head football coach at Ole Miss. Cutcliffe had success at Ole Miss, where he recruited Eli Manning, son of Ole Miss player Archie Manning, to play quarterback. In 2003, Cutcliffe's Rebels tied LSU for the Southeastern Conference West Division title, and they won the Cotton Bowl Classic.
Cutcliffe was fired by Ole Miss Athletic Director Pete Boone in December 2004 after his only losing season at Ole Miss. Boone had asked Cutcliffe to fire some assistant coaches and provide a detailed plan for improving the program, specifically the defense and recruiting. Cutcliffe refused to fire any staff members, and was subsequently fired along with his assistants.
After his stint at Ole Miss, Cutcliffe was hired by head coach Charlie Weis as the assistant head coach and quarterbacks coach at Notre Dame, but health problems forced him to resign before his first season there. In 2005, he underwent successful triple-bypass surgery to correct a 99-percent blocked artery. After taking a year off he returned to Knoxville to coach Tennessee again and join his sons, Chris Cutcliffe and Marcus Hilliard, then Tennessee students, on campus (his oldest daughter, Katie Cutcliffe Kolls, would also attend Tennessee). After Cutcliffe's successor as offensive coordinator at Tennessee, Randy Sanders, resigned, Phillip Fulmer rehired Cutcliffe to replace him.
Cutcliffe led a major turnaround of the Tennessee offense during the 2006 season. Tennessee quarterback Erik Ainge ranked among the nation's top 25 passers by yardage, and Robert Meachem had the third-most receiving yards of any player.
Cutcliffe was hired as the head football coach at Duke University on December 14, 2007, replacing Ted Roof, who had amassed a 6–45 win-loss record (3–33 in the ACC) over four-plus years at the school. Cutcliffe inherited a program that had tallied only three winning seasons in the last 25 years and, before the 2008 season, had not beaten an ACC opponent in over three seasons.
Cutcliffe immediately began a strength and conditioning program, challenging the team to collectively lose 1,000 pounds after finding the team in less than ideal physical shape.
On Saturday, August 30, 2008, Cutcliffe won his first game as Duke's head coach, defeating the James Madison Dukes 31–7, before a crowd of 32,571, the largest in Wallace Wade Stadium since 1994. The game marked the introduction of a number of rituals that Cutcliffe hopes to turn into Duke traditions, including the Blue Devil Walk, which parades the players and coaching staff from Duke Chapel, through West Campus and past Cameron Indoor Stadium to Wallace Wade Stadium, and the "Blue Devil Rock", located in the stadium tunnel and mined from the same quarry used in the construction of Duke's West Campus.
In Cutcliffe's second game, Duke lost to Northwestern in a mirror image game of the previous season's matchup, twice falling short of a touchdown deep in Northwestern territory. After the home loss against Northwestern, Duke hosted Navy, prevailing 41–31. Cutcliffe next led Duke to its first ACC victory since 2004, with a 31–3 rout of Virginia. This was a complete turnaround from the team's 2006 game against UVA, in which the Blue Devils were shut out 37–0 in Wallace Wade. Duke proceeded to lose to Georgia Tech and Miami before notching its first road win of the season, a 10–7 victory over SEC opponent Vanderbilt. Next, on the road at Wake Forest, Duke lost in overtime, 33–30, missing what would have been a game-winning field goal at the end of regulation. This was another in a string of such painful kicking miscues for the Blue Devils, including a miss at North Carolina in the previous season. The next game, Duke went on to lose to Clemson, 31–7, before fighting to a surprisingly close 14–3 loss to powerhouse Virginia Tech and suffering a disappointing close loss to arch-rival North Carolina at season's end.
In January 2010, following Lane Kiffin's abrupt departure after just one season at the helm of the Tennessee football team, Cutcliffe quickly emerged as a leading candidate to replace Kiffin. Cutcliffe, however, ultimately rebuffed Tennessee's overtures, remaining at Duke and stating, “After much thought and consideration, Karen and I reached the decision that Duke is the place for our family. We have both family members and lifetime friends in the Knoxville community and share a deep respect for the University of Tennessee. Our ties to the school and the Eastern Tennessee area are obvious. But before Tennessee’s hiring process comes to a conclusion, I know that Duke University is where we want to coach.” Cutcliffe's decision was widely lauded as a rare example of commitment and integrity among prominent college football coaches.
On October 20, 2012, Coach Cutcliffe led the Devils to their first win over North Carolina since 2003. In doing so, Duke became bowl eligible for the first time since 1994. He was subsequently named ACC Coach of the Year on November 27, 2012.
On October 26, 2013, Cutcliffe led the Blue Devils to an upset of #14 Virginia Tech, 13–10. This was Duke's first win over a ranked opponent since beating #14 Virginia in 1994. With this win, the Blue Devils became bowl eligible for a second consecutive season for the first time since the 1988 and 1989 seasons. On November 29, with a close 27–25 win over North Carolina, the Blue Devils clinched their first-ever Coastal Division title and a berth in the 2013 ACC Championship Game falling to the eventual National Champions Florida State Seminoles and Heisman Trophy winner Jameis Winston 45-7. Duke also had its first 10-win season in the school's over 100-year history of football. Duke's historic 2013 season concluded on New Year's Eve in Atlanta, GA, at the Chick-fil-A Bowl against the Texas A&M Aggies, led by 2012 Heisman Trophy winner Johnny Manziel. In a high-scoring affair totaling 100 points, Duke took a 38–17 halftime lead before ultimately succumbing to a Manziel-led rally, 52–48.
Six quarterbacks whom Cutcliffe coached in college have gone on to play in the NFL: Heath Shuler, Peyton Manning, Eli Manning, Erik Ainge, Thaddeus Lewis, and Sean Renfree.
Cutcliffe also coached former Colorado Rockies first baseman Todd Helton while Helton played quarterback at Tennessee. Eli Manning's former backup, Seth Smith, plays for the Seattle Mariners.
Cutcliffe is married to Karen Cutcliffe. They have four children: Marcus, Chris, Katie and Emily.
Assistant coaches under David Cutcliffe who became NCAA head coaches:Jim Knowles: Cornell (2004–2009)
Mike MacIntyre: San Jose State (2010–2012), Colorado (2013–present)
Scottie Montgomery: East Carolina (2016–present)