Desmond Roland added 44 yards and a touchdown on 16 rushes for the Cowboys (8-1, 5-1 Big 12), who won their fifth straight game. Roland also had a 19-yard reception for a score early in the second quarter that gave OSU a 21-0 lead.
Montell Cozart threw for 58 yards while rushing for 55 on 18 carries for Kansas (2-7, 0-6), which lost its sixth in a row. Tony Pierson returned from a three-game absence due to a concussion and gained 87 yards on six rushes. James Sims added 66 yards rushing and 13 yards on three receptions.
Oklahoma State jumped on top immediately, as Justin Gilbert zig-zagged his way to a 100-yard touchdown on the opening kickoff.
Aided by a Kevin Peterson interception and subsequent 38-yard return, the OSU offense made it 14-0 on Roland's 3-yard run with 8:28 left in the first quarter.
The Jayhawks' first chance for points came early in the second when Ron Doherty lined up for a 32-yard field goal attempt, but the ball clanked off the left upright.
Oklahoma State responded by driving 80 yards the other way in just four plays, as Chelf connected with a wide open Roland for the 19-yard TD pass with 9:25 remaining in the first half.
The Cowboys extended their advantage to 28 points with just 15 seconds left before halftime, when Chelf lofted a fade pass to the left corner of the end zone, where a leaping Tracy Moore held on for a 4-yard touchdown.
Kansas finally got on the scoreboard midway through the third quarter on Doherty's 40-yard field goal.
Following another perfect fade pass from Chelf to Tracy Moore for an 11-yard touchdown early in the fourth, Doherty's 29-yarder made it 35-6.
Over 50 members of the 1988 Oklahoma State team that went 10-2, including Heisman Trophy winner Barry Sanders and current Cowboys coach Mike Gundy, were honored on the field during halftime.