Perry entered the last round a shot behind Kirk Triplett but made his way to the top with steady play in a bogey-free round that put him at 16-under-par and gave him a two-stroke win.
The victory was Perry's fourth major title on the Champions Tour. He also won the US Senior Open in 2013.
“It's our goal to always win our championship," Perry told reporters. "This trophy goes back a long way.”
Brandt Jobe finished third at nine under while Tom Lehman and Fred Couples were tied at eight under.
Perry’s win broke the major dominance of German Bernhard Langer, who had won the year’s first two major titles but finished tied for 18th this week.
Perry birdied his first hole of the day and grabbed full command by the par-5 sixth where he made birdie for a two-stroke advantage.
