The pole-sitter passed Kevin Harvick with about 21 laps left in the 200-lap race on the one-mile oval when Harvick got caught in traffic with Amber Cope, who was 30 laps down.
Keselowski, also entered in Sunday's Sprint Cup race, stretched it from there and won by just over seven-tenths of a second. He also won the pole the last two years in Nationwide races in New Hampshire, but Kyle Busch won both times.
Busch had trouble with his fuel cell Saturday and was never in contention.
Austin Dillon finished third, followed by Sam Hornish Jr. and Ricky Stenhouse Jr.
Rounding out the top 10 were Kasey Kahne, Elliott Sadler, Justin Allgaier, Jamie McMurray and Ryan Truex.