Unable to finish drives in the first half, Richardson and the offense got rolling in the second and gave the Cyclones (2-4) a much needed victory in a rare October break from Big 12 play.
Toledo (4-2), which had a three-game winning streak broken, ran the ball well and pulled into a 23-23 tie in the fourth quarter. But the Cyclones took the lead on Richardson's 5-yard TD pass to E.J. Bibbs and secured the victory with a 16-play, 85-yard drive that Richardson finished with a 14-yard scoring pass to Alan Lazard, making it 37-23.
Richardson finished with a school-record 37 completions in 53 attempts and connected with nine different receivers, including a lineman.
The back-and-forth game wasn't unexpected. Toledo came in averaging 516 yards a game - 17th nationally - but the Rockets were giving up 326 yards a game passing, and Richardson's receivers found plenty of space in the secondary.
Lazard, a freshman, had season bests of eight catches for 96 yards. D'Vario Montgomery caught nine balls for 90 yards, both career bests.
Richard's previous best had been 262 yards against Texas last year. The old school record for completions was 36, shared by Austen Arnaud and Steele Jantz.
Toledo played its third straight game without running back Kareem Hunt, who leads the nation with 8.9 yards a carry. The Rockets got 124 yards in 17 carries and two touchdowns from freshman Terry Swanson, but he was held to 18 yards on five second-half rushes.
Swanson's 1-yard touchdown dive and Jeremiah Detmer's 41-yard field goal, his third of the game, pulled Toledo into the tie at 23 early in the fourth quarter after Iowa State had built a 10-point lead with two crisp drives to open the second half.
With the Cyclones trailing 13-9, Richardson hit Tad Ecby with a perfectly thrown 23-yard pass to the end zone. Iowa State's defense forced a quick three-and-out and the offense responded again, moving 65 yards in 10 plays to go up 23-13.
The officials ruled Richardson had scored on a 3-yard run, but the call was reversed on review, the replay showing his knee was down just inside the 1. It became moot when Martinez Syria stormed into the end zone on the next play.
Iowa State put together good drives on three of its four first-half possessions, but couldn't finish any of them and had to settle for Cole Netten field goals of 32, 36 and 37 yards.
The 36-yarder put ISU up 6-3 and came after the Cyclones marched to a first-and-goal at the 3, only to be set back by Richardson's 3-yard loss on a keeper, an incompletion and a pass that guard Daniel Burton caught, resulting in a 12-yard loss.
Toledo answered with its best drive of the half. The Rockets went 4-for-4 on third-down conversions during a 14-play, 75-yard drive that ended when Swanson weaved 14 yards through the defense and leaped into the end zone.