Stenhouse had a strong car all day and dominated the end of the 200-mile race, pulling away from Mark Martin on a pair restarts on the 1.5-mile tri-oval in the desert.
Martin, who had won four of his previous six Nationwide starts at Las Vegas, finished second in his first Nationwide race for Joe Gibbs Racing. Polesitter Elliott Sadler rallied to finish third after a lengthy mid-race pit stop to fix a vibration.
Danica Patrick was 12th in the first race at LVMS since IndyCar star Dan Wheldon was killed in a fiery crash last fall.
Stenhouse was the top Nationwide rookie in 2010 and earned the season championship last year after winning two races and posting 26 top-10 finishes. He opened this season by finishing 19th at Daytona after being caught up in a late wreck and entered Saturday's race fifth in points after taking third at Phoenix last week.
Stenhouse started sixth at Las Vegas and stayed near the front, taking the lead with 54 laps left. He pulled away from Martin out of two cautions down the stretch and had a big cushion when he crossed the checkers.
Martin was in the No. 18 Toyota that Kyle Busch drove in 38 of his series-record 51 wins before moving on to start his own team. The 53-year-old Martin was solid in the middle of the race, leading 44 laps and stayed near the front, but didn't have enough to keep up with Stenhouse.
Patrick was back at LVMS for the first time since Wheldon was killed in IndyCar's 2011 season finale.
The two-time Indy 500 champion died on Oct. 16 when his car was involved in a 15-car pileup on the 12th lap and sailed into a catch fence, where his head struck a pole.
Patrick watched the wreck unfold in front of her and narrowly missed becoming involved. So instead of a triumphant departure from IndyCar, she headed off to NASCAR dejected after seeing a friend die in front of her.
Patrick was somber when she arrived at LVMS on Friday, saying the walk from the garage back to the media center brought back a flood of memories.
She was able to keep her emotions in check once inside the car, though, putting together a decent qualifying run to start 12th in Saturday's race.
Patrick struggled early, dropping toward the back of the pack before starting to move up. She made a daring pass around lap 60, ducking under two cars to move up to 16th, and was 10th coming out a caution near the race's midpoint.
Patrick moved up to sixth, but fell back a few spots on a restart with about 50 laps left and never made up the ground.
Sadler was strong early, but the team decided to lift the hood to fix his car after he complained of vibrations midway through the race. He returned to the track 20th and made his way back through the field to pull out a solid finish after breaking a 14-year winless streak in the Nationwide series last week in Phoenix.
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