Senior guard Je'Kel Foster led the Buckeyes (7-0) with a career-high 28 points. He was a blistering 6 of 8 from 3-point range.
"I don't think I've ever been so proud of a team," Ohio State coach Thad Matta told WBNS-AM. "To get down like we did… This is a very good basketball team that we beat tonight and I give our guys credit."
Led by 6 of 6 shooting from freshman forward Shawn Taggart, the Cyclones (6-3) took a 39-32 lead at halftime. Foster led OSU with 12 points in the first half on 4 of 5 shooting from long range.
Ohio State opened the second half with a 16-5 run and the Buckeyes took a 48-45 lead on a 3-pointer from Lewis at the 13:56 mark.
However, Iowa State responded with a 15-4 run to take a seemingly commanding 60-52 lead with 6:39 left in the game. The crowd at the Wells Fargo Arena, which opened for business this weekend, was beginning to get rowdy. (Des Moines is located 40 miles south of ISU's campus in Ames.)
But the Buckeyes would not die. J.J. Sullinger capped a 7-0 OSU run with a free throw to cut Iowa State's lead to 60-59 with 3:20 remaining.
A basket from Will Blalock gave the Cyclones a 62-59 lead with 2:57 left on the clock. But a long jumper from Foster, followed by a driving basket from Lewis gave Ohio State a 63-62 lead at the 1:36 mark.
Curtis Stinson then connected on a pair of free throws to give ISU a 64-63 lead with 1:08 remaining.
Foster responded with two free throws and the Buckeyes regained the lead at 65-64 with 1:02 showing on the clock.
Following an Iowa State miss and a Lewis rebound, Ohio State guard Jamar Butler was fouled and made both ends of the one-and-one for a 67-64 OSU lead with 30.8 seconds left in the game.
A Lewis free throw with 13.3 seconds left was the proverbial nail-in-the-coffin and the Buckeyes escaped with a big road victory.
Matta went to a zone defense in the second half which helped cool off the Cyclones.
"I was telling our guys at halftime that I didn't think Iowa State could play better than they did," Matta said. "The adjustment to go zone in the second half really proved to be the game."
Ohio State came up clutch late in the game, but the Buckeyes were sloppy for most of the way.
"In the first half, I think we missed six lay-ups," Matta lamented.
But a star has emerged in the 6-2 Foster. The former junior college All-American continues to impress.
"Unbelievable," Matta said of Foster's performance. "And I've said this I don't know how many times, he deserves it, because he works so very hard. He does such a tremendous job every single day.
"You think about this stretch these guys have been on with four games in seven days and I couldn't be prouder of them."
The 6-4 Lewis is developing a reputation as a clutch, second-half performer. His game against Iowa State mirrored his performance last week in OSU's win over St. Joseph's.
"We got him lower and got some match-ups there in the second half," Matta said of Lewis. "We knew on that side of the floor was the big guy and we were hoping, as it played out, that he would have a tough time keeping Ron in front of him."
Stinson led Iowa State with 17 points.
The win gave No. 25 OSU its first 7-0 start since the 1990-91 season.
Ohio State gets back in action Friday, Dec. 23 at home against Tennessee State (8 p.m.)