Chelf passed for 229 yards in his second career start. J.W. Walsh, who had what coach Mike Gundy called a season-ending injury four weeks ago, ran for one touchdown and threw for another out of a short-yardage package.
Seth Doege threw for 230 yards with two interceptions and a single touchdown pass for Texas Tech (7-4, 4-4). He started the day leading the Bowl Subdivision with 34 touchdown passes this season.
The Red Raiders had a chance to pass the defending conference champions in the Big 12 standings, and perhaps secure a better bowl destination, but instead dropped their fifth straight game in Stillwater.
During a pregame ceremony, Oklahoma State observed a moment of silence to mark the one-year anniversary of the plane crash that killed women's basketball coach Kurt Budke, assistant Miranda Serna and two others.
The Cowboys had expected big things out of Anderson after a strong training camp, but he had been limited so far this season by an injury. He was one of the team's most experienced receivers, with the departure of first-round NFL draft pick Justin Blackmon and Josh Cooper, who also ended up in the NFL.
Anderson was on the receiving end of scoring passes of 60, 33 and 66 yards from Chelf and ended up with nearly three times his previous career-best of 64 yards receiving in a game.
Sparked by a series of big plays on defense and special teams, Oklahoma State's offense got clicking to break the game open with 28 consecutive points in the second quarter.
The Cowboys sacked Doege three times in the first half and Tyler Johnson was pressuring him again to force an ill-advised throw that Shamiel Gary intercepted. Just two plays later, Chelf connected with Anderson on a 33-yard flea flicker pass to push the Oklahoma State advantage to 21-7.
Tech couldn't respond and followed that by going three-and-out, with Craig rushing in to block Ryan Erxleben's punt and keep Oklahoma State's roll going. Walsh finished the ensuing drive with a 2-yard TD run on a quarterback keeper, and Chelf threw his 66-yard touchdown pass to Anderson on the first play after another Red Raiders three-and-out.
Doege threw a 2-yard TD pass to Tyson Williams with 15 seconds left before halftime, and the Red Raiders got the ball to start the second half. But Doege's second interception - directly into the arms of retreating defensive tackle James Castleman - ended that drive and any momentum for Tech.
Joseph Randle and Jeremy Smith each tacked on touchdown runs for Oklahoma State in the second half, and Quinn Sharp matched his career-long with a 51-yard field goal. Craig's punt block extended the lead to 59-14 early in the fourth quarter.
Darrin Moore caught a late 7-yard touchdown pass from backup Michael Brewer and finished with 140 yards receiving for Texas Tech.