He parred the last to shoot a 70 and finish at seven-under-par 277, one ahead of American Kevin Na at the Copperhead course at Innisbrook in Palm Harbor, Florida.
“This is the biggest win over here I’ve ever had,” Senden told Golf Channel.
“My first PGA Tour win (at the 2006 John Deere Classic) was special but this you’ve got stronger players in the field and it’s a real feather in the cap to know you’ve beaten a quality field.”
Six players were within one stroke of the lead late in the final round before Senden emerged for his second PGA Tour victory and his first anywhere since the 2006 Australian Open.
The 42-year-old earned $1.026 million and a Masters invitation.
Senden, twice a runner-up at Innisbrook, looked destined for another near-miss when he made three bogeys in four holes from the 12th as a combination of nerves and demanding conditions conspired to cause a series of uncharacteristic poor shots.
But he gave himself a pep talk as he approached his ball in the rough short of the 16th green.
“I said something special’s got to happen here if you’re going to get it done,” he said. “I’ve been working really hard on that particular shot out of the long grass and (it was) lucky enough to go in the hole.
“Then I made a couple of really solid swings the last two holes. I’m just so happy to come out on top.”
Na birdied the par-three 17th after almost making a hole-in-one but could only par the last in gusty winds.
The American plunged off the leaderboard after dropping four shots in three holes before the turn, but showed resilience to battle all the way back to finish runner-up with a 72.
“It was a bad string of holes but I settled down, got back right in it,” Na said. “It was playing tough and I made two great birdies coming in but it wasn’t good enough.”
Left-handed Scott Langley, who held a share of the lead with three holes left, had a 70 to finish third, two shots behind.
Overnight leader Robert Garrigus was another shot back, equal fourth. He dropped five shots in the first six holes before steadying.
(Reporting By Andrew Both in Cary, North Carolina, editing by Gene Cherry)