Iowa State (2-7, 0-5) has lost seven straight. The Cyclones' most effective player was Leonard Johnson, who had kickoff returns of 72, 73 and 48 yards en route to setting the major college record for kickoff return yards with 319 on nine returns.
Bryant entered the game ranked third in the Football Bowl Subdivision in receiving yards per game (110.4) and touchdown receptions (11). He now has 1,054 receiving yards this season, the fifth-best single-season total in Oklahoma State history, with at least four games remaining.
Bryant, who earlier this season had three touchdown catches in wins over Troy and Texas A&M, is only two shy of matching the single-season school record of 17, set by Rashaun Woods in 2002.
Robinson finished 18-of-27 passing with five touchdowns, including a 95-yard third-quarter scoring pass to Jeremy Broadway that was the longest pass play in school history.
Robinson's 395-yard passing outing was the fourth-best ever at Oklahoma State and his 461 yards of total offense was second-best in school history. He had 486 yards of total offense against Texas last season.
The Cowboys, who lost 28-24 a week earlier at No. 1 Texas, finished with 682 yards of offense, fifth-best in school history.
Iowa State quarterback Austen Arnaud completed 20 of 35 passes for 240 yards with two interceptions and one touchdown.
Oklahoma State fullback Bryant Ward scored on a 1-yard run on his first career carry to put the Cowboys ahead less than 5 minutes into the game.
The 72-yard kickoff return by Johnson set up a 1-yard touchdown run by Alexander Robinson. The Cyclones then recovered an onside kickoff, only to have it nullified by an offside penalty. Oklahoma State took the lead for good with the 11-yard touchdown pass from Zac Robinson to Bryant.
In the second quarter, Bryant outjumped Iowa State cornerback Ter'ran Benton in the end zone to complete the 26-yard scoring pass from Zac Robinson.
The Cyclones drove to the Oklahoma State 12 before Terrance Anderson intercepted Arnaud in the end zone, and on the next play, Robinson hit a wide-open Bryant -- who was five yards behind the nearest defender -- for an 80-yard touchdown. At the time, it was the Cowboys' longest pass play since 1992.
After Johnson returned the ensuing kickoff 73 yards to the Oklahoma State 27, Grant Mahoney pulled the Cyclones to 28-10 with a 38-yard field goal with 4:02 left in the half.
Oklahoma State built on that lead just three plays and 54 seconds into the third quarter on a 36-yard touchdown run by Kendall Hunter, who carried 13 times for 104 yards.
The 95-yard Robinson-to-Broadway pass broke by 10 yards the record for the Cowboys' previous longest pass. Bob Cutburth connected with Hermann Eben on an 85-yard pass against Kansas State in 1969 and a pass from Earl Wheeler to Curtis Mayfield against Nebraska in 1985 matched that mark.