"I'm very appreciative for the 10 years of loyal service that Glenn Spencer gave to Oklahoma State," Cowboys head coach Mike Gundy said in a brief statement.
Spencer began coaching at Oklahoma State in 2008 as a defensive line coach. He served as co-defensive coordinator in 2011 and 2012 and was named the sole defensive coordinator January 2013.
The Cowboys were ranked 14th in final AP poll after beating Virginia Tech 30-21 in the Camping World Bowl.
Oklahoma State ranked 85th nationally in scoring defense, allowing 29.4 points per game, but that was good enough to rank sixth in the Big 12.