The win extended TCU's winning streak to 10 games, the third-longest in the nation behind No. 1 USC (34) and No. 2 Texas (19).
LoCoCo's field goal was TCU's only score in the second half after the Horned Frogs built a 24-17 halftime lead.
The Mountain West champion Horned Frogs were out to prove themselves after being snubbed by the BCS. TCU has the best record among teams from non-BCS conferences.
The win gave TCU (11-1, 8-0) 11 victories for the fourth time in school history and the first time since 2003.
It was an sloppy game with four fumbles, three interceptions and 20 penalties.
Quarterback Jeff Ballard improved to 8-0 as a starter by throwing for 275 yards and a touchdown, despite being sacked six times.
TCU had a chance to go ahead early in the fourth quarter, but running back Robert Merrill fumbled at the 1-yard line after a 21-yard run, and Iowa State recovered.
Bret Meyer threw a 22-yard touchdown pass to Todd Blythe to move Iowa State (7-5, 4-4 Big 12) into a 24-all tie in the third quarter. Blythe lost his helmet following the diving catch. The score was Blythe's school-record ninth touchdown reception of the season.
Meyer was 20-of-33 for 254 yards and three touchdowns.
TCU didn't seem rusty, even after a 49-day layoff since its last game. The Horned Frogs jumped out to an early lead when Merrill was untouched on a 20-yard scoring run that capped an 80-yard drive on the team's first series.
Merrill finished with 11 carries and 109 yards.
The Horned Frogs extended their lead to 14-0 when Aaron Brown scored on an 7-yard run that followed an Iowa State fumble.
Iowa State had just 21 yards in the first quarter, but took advantage of TCU mistakes to score 17 unanswered points to take the lead in the second quarter.
On the last play of the first quarter, Iowa State's LaMarcus Hicks got in front of TCU's Cory Rodgers to make his fifth interception of the season. Two plays later, Blythe outran TCU's Drew Coleman and grabbed a 48-yard touchdown pass from Meyer. It was the first touchdown allowed by the Horned Frogs in 10 quarters.
On the ensuing series, TCU punter Brian Cortney chased a high snap out of the back of the end zone for an Iowa State safety.
Meyer shook off two would-be tacklers before scampering for a career-long 39 yards to the 6. On third down, he found Jon Davis in the corner of the end zone with a 6-yard touchdown pass, and then hit a wide-open Ben Barkema for the 2-point conversion for a 17-14 lead.
A fumble by Meyer set up a bowl-record, 84-yard touchdown reception by Michael DePriest that put TCU back on top. Chris Manfredini kicked a 30-yard field goal just before halftime to leave the Horned Frogs ahead 24-17.
It was the second time TCU has faced a Big 12 team this season. The Horned Frogs beat then-No. 7 Oklahoma in their season opener.
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