Fickell spent his entire playing career in Columbus, Ohio, graduating from DeSales High School in 1992. After redshirting for the Buckeyes in 1992, Fickell went on to be a standout member of the defensive unit, making a school-record 50 consecutive starts at the nose guard position from 1993–1996, four bowl games. In his freshman year, he lined up next to Dan Wilkinson. Despite having a torn pectoral muscle, Fickell started the 1997 Rose Bowl, making two tackles in the Buckeyes victory over Arizona State. After graduating from Ohio State in 1997, Fickell signed as an undrafted free agent with the New Orleans Saints. After tearing the ACL in his knee, he spent the remainder of the season on the injured reserve list and was later released by the team.
After his brief stint in the NFL, Fickell fulfilled a childhood dream by joining the Ohio State Buckeyes coaching staff after being accepted as a graduate assistant with the Buckeyes in 1999 under his former coach, John Cooper. In 2000, Fickell was hired by the University of Akron as the defensive line coach. After two seasons with the Zips, he returned to Ohio State once again in 2002, this time as the special teams coordinator under second-year head coach, Jim Tressel. In 2004, Fickell took over as the linebackers coach, adding the title co-defensive coordinator to his responsibilities in 2005. In 2010, He was named Assistant Coach of the Year by the AFCA, joining a list of Buckeyes coaches to be recognized by the association that also includes Carroll Widdoes, Woody Hayes, Earle Bruce and Jim Tressel.
Fickell was initially promoted to the position of assistant head coach and was to serve as the interim head coach during Jim Tressel's five game suspension to open the 2011 season. However, on May 30, 2011, Tressel resigned amid an NCAA investigation and Fickell was appointed to the position of head coach. On November 28, Fickell's stint as head coach ended with the hiring of Urban Meyer. He coached the Buckeyes one last time in the 2012 Gator Bowl against Meyer's old team, the Florida Gators. Although only achieving a 6-7 record, many analysts praised Fickell's leadership and handling of players during the 2011 season. On January 15, 2012, Luke Fickell was introduced as Urban Meyer's co-defensive coordinator.