The Colombian started from pole and was among the leaders throughout before winning from Team Penske team-mate Helio Castroneves at the Pocono Raceway.
Montoya led 45 laps and took the lead for good on the 197th when Tony Kanaan had to pit late in the 200-lap race.
In his first season in IndyCar since 2000, former Formula One driver Montoya was delighted to be back winning.
"I want to thank Roger (Penske) for believing in me after so many years out of an Indy car," Montoya said.
"This is fantastic. Things were going good, but you never know when you're going to get a win. We did the right things and got the win, and we're at a good place at this point of the season."
Andretti Autosport driver Carlos Munoz finished third, ahead of Ryan Briscoe (Chip Ganassi Racing), Scott Dixon (Chip Ganassi Racing) and Simon Pagenaud (Sam Schmidt Motorsports).
Team Penske's Will Power, who was 10th on Sunday, still sits top of the championship, but Castroneves is now level with him on 446 points.
Pagenaud (402 points), Montoya (391) and Andretti Autosport driver Ryan Hunter-Reay (388) make up the top five.