The Wildcats, in the middle of a three-game losing streak, have a 4-5 record with games remaining at Missouri and home games against Nebraska and Iowa State the following two Saturdays.
KSU has surrendered 110 points in its last two games, and after last Saturday's 56-21 loss to in-state Big 12 Conference foe Kansas, is ranked 107th in scoring defense.
Prince went 0-3 against the Jayhawks.
"We are in a performance-based profession and have made this decision in the best long-term interest of both the university and its football program," KSU athletic director Bob Krause said in a statement.
In his tenure, Prince has a 16-18 record, including 7-6 in 2006, his first season in Manhattan.
The Wildcats finished 2006 with a trip to the Texas Bowl.
Krause said earlier this week, Prince will receive a $1.2 million buyout.