Athletic director Charles McClelland announced the move, saying: "We have agreed that Coach Cole's separation from the program is best for all parties."
McClelland said the school anticipates "major NCAA violations toward our football program with regards to recruiting, unethical conduct and academic inconsistencies among other things."
The NCAA has been investigating after an academic review turned up possible violations
Defensive coordinator Kevin Ramsey will serve as interim head coach, and the university will hire a permanent replacement after the 2011 season.
Cole went 19-16 in three seasons, including a 9-3 record and the Southwestern Athletic Conference championship in 2010, the school's first outright conference title.
"We've had good success," Cole told KRIV-TV in Houston. "We've graduated students, we've won a championship, and we've done it the right way. I have not resigned, but I have been relieved of duty, and I intend to get that worked out."
McClelland said in January that the NCAA randomly selected the school for a review of its academic program performance data covering 2004-07, which was prior to McClelland's or Cole's hiring, and discovered inconsistencies in the materials.
In a letter obtained by the Houston Chronicle on Jan. 19 through an open-records request, the NCAA told Texas Southern that it had possibly uncovered additional violations in the men's basketball and football programs.
