Applewhite went 8–2 as a starter, including upsets of #7 Nebraska 20–16, which broke the Cornhuskers' 47-home game winning streak, and #6 Texas A&M.

He capped the season by leading the Longhorns to a 38–11 victory over the Mississippi State Bulldogs in the Cotton Bowl Classic.

Simms struggled early and Applewhite got the majority of the snaps in what turned out to be a rout, thus regaining the starting job.

His second pass was completed for a 79-yard touchdown and he baited the University of Colorado bench in an attempt to rally the Texas fans.

[6] His near miracle comeback, combined with Simms' injury, earned him the starting position for his final game at Texas, the 2001 Holiday Bowl and he didn't disappoint.

After graduation, Applewhite was signed by the New England Patriots days after the 2002 NFL draft,[7] but quit prior to the start of camp to finish his degree and to pursue a career in coaching.

[10] Graham said of Applewhite's expected contribution to the new staff, "We want to spread the field and throw the football, and every quarterback and receiver in this state will be interested in Rice with Major as our offensive coordinator.

[14] He did however leave Rice only a month later, not for Iowa State but for Alabama, as he accepted an offer by newly hired Crimson Tide head coach Nick Saban to serve as the offensive coordinator.

[15] Given his ties to the Lone Star State, Applewhite targeted a couple of Texas high school prospects, including Lennon Creer.

Alabama eventually received commitments by quarterback Nick Fanuzzi and defensive back Tarence Farmer.

Following a 41–17 blowout win over SEC rival Tennessee on October 20, Applewhite was named "Offensive Coordinator of the Week.

The next day, Mack Brown announced that the primary play caller and other co-offensive coordinator would be Bryan Harsin from Boise State.

[25] In early 2013, Applewhite admitted he was disciplined by the University of Texas for "having an inappropriate relationship with a student at the 2009 Fiesta Bowl.

Texas athletic director DeLoss Dodds reprimanded Applewhite by freezing his salary and requiring him to undergo counseling.

[28] In a public statement Applewhite commented on the affair: "Several years ago, I made a regretful decision resulting in behavior that was totally inappropriate.

"[29] The revelation occurred in the wake of investigation into Texas track coach Beverly Kearney's relationship with a student athlete.