Fickell started his playing career at St. Francis DeSales High School, where he was a two-time first-team All-Ohio defensive tackle as well as a three-time state champion in wrestling.

[1] After redshirting for the Buckeyes in 1992, Fickell was a standout defensive player, making a school-record 50 consecutive starts at the nose guard position from 1993 to 1996.

After graduating from Ohio State in 1997, Fickell signed as an undrafted free agent with the New Orleans Saints of the National Football League (NFL).

[2][3][4] After a brief stint in the NFL and at Ohio State as a graduate assistant in 1999,[5] in 2000 Fickell was hired by the University of Akron as the defensive line coach.

[10] In 2011, Fickell was originally named to serve as interim head coach in place of Jim Tressel, who was given a five-game suspension by the NCAA due to a recruiting scandal.

Both teams went into the game down a number of key players due to injury, illness, or opt-outs, including Cincinnati's two All-Americans Sauce Gardner and James Wiggins.

In 2021, Fickell again led the Bearcats to a perfect regular-season record, including non-conference wins at the Notre Dame Fighting Irish and the Indiana Hoosiers.

With a record of 13–0 as the only undefeated team in the nation, Cincinnati was selected as the #4 seed in the College Football Playoff, making them the first program outside of a "Power 5" conference to advance.

[41] Later on Cincinnati would go on to lose the College Football Playoff Cotton Bowl Semifinal to the University of Alabama and Head coach Nick Saban falling to them 27–6.

[45][46][47] Fickell was credited with coaching and winning his first game only several weeks after being hired, replacing interim Jim Leonhard in title for the 2022 Guaranteed Rate Bowl.

Luke Fickell and his wife, Amy (Goecke), who has a physical therapy degree from Ohio State, have six children—five sons and one daughter—including two sets of twin boys.

[58] Fickell's eldest son, Landon, committed to Cincinnati as an offensive guard out of Moeller High School as part of the 2021 recruitment class.