Lane Kiffin worked as a Graduate Assistant for one year at Colorado State University. Kiffin joined the University of Southern California (USC) staff in 2001. Between 2002-2005, he was used in many roles including the wide receivers coach, the passing game coordinator, and the offensive coordinator. During Kiffin's tenure with USC, he was instrumental in the development of several wide receivers and tight ends in the program. 

Under Kiffin in 2005 the USC offense produced school records in virtually every dimension, averaging 49.1 points and 579 yards per game. USC’s potent offense that season became the first in NCAA history to have a 3,000 yard passer (Matt Leinart), two 1,000 yard rushers (Reggie Bush and LenDale White), and a 1,000 yard receiver (Dwayne Jarrett). In Kiffin’s three years as recruiting coordinator at USC, the Trojans had the No. 1 ranked recruiting class in college football every year. 

The Oakland Raiders hired Kiffin on January 23, 2007, making him the youngest head coach in Raiders history (31), and the youngest head coach in the NFL's "modern era" (i.e. since 1946). On November 28, 2008, multiple media outlets reported that Lane Kiffin would be the next head football coach for the University of Tennessee Volunteers in 2009. UT formally introduced Kiffin as the school's 21st head football coach on December 1, 2008. Kiffin, 33, was hired by Tennessee and became the youngest active head coach in Division I FBS.

Kiffin led the Vols to a 7-6 record in 2009, an improvement from their 5-7 record in 2008. The Vols increased their offensive output by more than 60 percent in 2009 with Kiffin calling the offensive plays. After one season as coach, Kiffin left the Vols during the 2010 recruiting season to accept the head coaching job at the University of Southern California. He coached USC until 2013 and was named offensive coordinator by Nick Saban for the University of Alabama in 2014.