Quarterback Clint Chelf had 163 total yards in his second start of the season for the Cowboys (6-1, 3-1 Big 12), who ran for a season-high 342 yards.
Oklahoma State scored 14 points in a 2-½ minute stretch late in the third quarter to extend its lead to 45-20. Roland ran 58 yards for his third touchdown of the day, and Tyler Johnson took a fumble 54 yards for a TD with 4:17 left in the third.
Sam Richardson had 95 yards passing and a touchdown for Iowa State (1-6, 0-4) before leaving the game late in the first half after an apparent blow to the head.
After a blistering start, Oklahoma State let Iowa State sneak back into the game by halftime.
The Cowboys blew past the hapless Cyclones with a dominant third quarter.
Roland broke at least four tackles during his 58-yard TD run, the longest of his career, to put Oklahoma State up 38-20.
Cowboys linebacker Joe Mitchell then stripped Ernst Brun, and Johnson deftly maneuvered through a crowd of Cyclones and found the pylon for a back-breaking score.
Chelf, who got the starting nod over J.W. Walsh, was just 10 of 26 passing for 78 yards. But he added 85 yards rushing and a touchdown for the Cowboys — who had 179 yards rushing in just the third quarter.
Iowa State was coming off the most lopsided loss in school history, having been throttled by No. 6 Baylor 71-7 last weekend in Waco.
The Cowboys made the Cyclones look just as bad in the first 10 minutes.
Roland opened the scoring with a 2-yard touchdown run, and Justin Gilbert made it 14-0 Cowboys by taking a Richardson interception back 31 yards.
Oklahoma State pushed its lead to 21-0 on an 8-yard TD pass from Chelf to Charlie Moore midway through the first quarter.
To that point, Iowa State had given up an astounding 92 points in the 69:15 dating back to the start of the Baylor game.
But instead of burying the Cyclones, the Cowboys allowed them to climb right back into it.
Quenton Bundrage caught TD passes of 22 and 20 yards — the first from Richardson, the second from backup Grant Rohach — to help Iowa State pull within 28-20 by halftime.
But there would be no repeat of 2011, when the host Cyclones stunned the Cowboys in double overtime and ruined their shot at a national title.
Rohach finished with 97 yards passing for Iowa State, which converted just 4 of 20 third downs and punted 11 times.