Tucker was the interim head coach for the Jacksonville Jaguars of the National Football League (NFL) for the final five games of the 2011 season.

[8] He signed a contract with the Hamilton Tiger-Cats of the Canadian Football League after graduation but fell ill during training camp due to chickenpox and was cut from the team.

In 2002, Tucker was the defensive backs coach as Ohio State won a national championship, and in 2004 he was made co-defensive coordinator.

[8] After the firing of Browns' head coach Romeo Crennel, Tucker was replaced by Rob Ryan.

[14] In the 2011 season, head coach Jack Del Rio put Tucker in charge of defensive play-calling, and the team quickly became the fourth highest rated in the NFL.

[15][16] On November 29, 2011, Tucker was named Jacksonville's interim head coach following the firing of Del Rio.

On February 12, 2020, Tucker earned the nickname “Midnight Mel”[citation needed] and resigned as Colorado's head coach to accept the same position at Michigan State.

[29] With the COVID-19 pandemic forcing a late start for Big Ten teams in the 2020 season, Tucker's Spartans made their debut on October 24, 2020.

Unranked to begin the 2021 season, Tucker's Spartans jumped out to a 8–0 start, including a come-from-behind win over in-state rival and No.

[36] The Spartans went on to defeat Pittsburgh in the Peach Bowl 31–21, marking MSU's first 11-win season since their Big 10 winning 2015 campaign.

[37] This decision caused considerable surprise among college football observers, as Tucker had a career record of 16–14 at the time.

[40] But after opening the season with wins over Western Michigan and Akron, the Spartans lost their next four games, against Washington, Minnesota, Maryland and Ohio State, all by double-digit margins.

[41] After ending the losing streak with a double-overtime home win against Wisconsin, the Spartans again lost by double-digits, this time to Michigan.

The season concluded with another double digit loss to Penn State and no bowl game for the second time in three years.

On September 10, 2023, USA Today published a story detailing alleged sexual harassment by Tucker of Brenda Tracy.

Tracy, a rape survivor and anti-sexual violence advocate, had visited Michigan State's campus several times to speak with the team.

[43] Michigan State suspended Tucker without pay later that day, with Harlon Barnett taking over as interim head coach.