The Steelers all but shut down the Colts in the first half, holding them to zero yards in the first quarter and sitting on a 16-3 lead at half-time after Najee Harris' six-yard touchdown run and three field goals from Matthew Wright.
It all changed in the third quarter as the Colts, playing their third game under interim coach Jeff Saturday, came alive.
First Jonathan Taylor ran in a touchdown four plays after an 89-yard kick-off return from Dallis Flowers, then Matt Ryan found Michael Pittman with a six-yard touchdown pass that put Indianapolis up 17-16.
But they could not make it stick. The Steelers responded with an 11-play, 75-yard scoring drive that stretched into the fourth quarter, retaking the lead through Benny Snell's two-yard touchdown run before rookie quarterback Kenny Pickett hit George Pickens for a two-point conversion.
The Colts had an opportunity to respond late on after converting a fourth down on the Pittsburgh 37 with two minutes remaining, only to waste 36 seconds between first and second-down plays, rushing the next play on third down before being stopped on the fourth.
The Steelers improve to 4-7 after winning two of their last three, while the Colts are 4-7-1.