Sam Bradford added three touchdown passes in a wild first half in which the Sooners (7-1, 4-1 Big 12) give up a 28-7 lead before taking control with 27 consecutive points of their own.
The capper was a 68-yard punt return touchdown by redshirt freshman Ryan Broyles that gave the Sooners a 55-28 halftime lead. That total matched the school record for points in a half, set in the second half of Oklahoma's 76-0 shutout of the Wildcats in 1942.
Josh Freeman threw for a career-high 478 yards for K-State, with all three of his touchdown passes coming as the Wildcats charged back to tie it at 28.
But with 8 minutes left in the half, the Sooners found time to score four touchdowns.
Murray caught a tiebreaking 10-yard pass from Bradford and also had a 4-yard touchdown run before Broyles' return.
Murray ended up running for 104 yards on 17 carries and making four catches for 63 yards, with two touchdowns each way. Chris Brown ran 20 times for 142 yards and one touchdown.
Bradford, who came in completing 71 percent of his passes, went only 13-for-32 for 255 yards. The 40 percent completion rate was the lowest of his career and only the second time more than half of his passes were incomplete.
Oklahoma looked as if it might cruise after snuffing out K-State's deceptive onside kick attempt after its first touchdown. After tailback Logan Dold threw an 8-yard touchdown pass to Deon Murphy on a trick play, kicker Brooks Rossman took a designed fall on his approach to the tee and backup Jared Parker kicked the ball instead.
The ball squirted loose momentarily before Jermaine Gresham pounced on it for the Sooners. Murray caught a 15-yard touchdown pass two plays later to make it 21-7, and Brown's 11-yard run stretched the lead to 21.
Freeman's second touchdown pass pushed him past Ell Roberson's school record for TDs in a career. Freeman now has 38 career touchdown passes and his passing total ranked only behind Chad May's 489 yards against Nebraska in 1993.
He also had two interceptions and nearly had a third on a fourth-and-goal pass from the 1-yard line in the fourth quarter that instead fell out of Oklahoma linebacker Keenan Clayton's hands.