The Cougars lost four of their last five games in 2018, including a 70-14 loss to Army in last week's Armed Forces Bowl. The team finished with an 8-5 record.
Applewhite lasted just two full seasons in Houston. He was hired as offensive coordinator and quarterbacks coach in 2015 and was promoted to head coach with one game remaining in the 2016 season.
The former Texas assistant and star defensive tackle Ed Oliver got into a heated confrontation in November after he forced the defensive tackle to remove his jacket that was strictly reserved for active players.
Applewhite's firing signals the second significant coaching change for the Cougars. Offensive coordinator Kendal Briles resigned following the crushing bowl defeat and was then hired by Florida State on Dec. 23.