Doyle edged home favorite Tom Watson by two shots for his 11th Champions Tour title and fourth major championship, finishing at 8-under-par 272 to become the third repeat champion in tournament history.
Watson, who led after the second and third rounds, managed only a 2-over 72 in the final round to end at 6-under-par 274.
Seeking his fifth major championship on the Champions Tour, Watson instead finished runner-up for the third time at the U.S. Senior Open. He bogeyed three holes on the front nine and two more on the back.
'I hit pretty good shots, but just didn't get the right feel today,' he said.
It was a tale of two players Sunday, more or less: the one with the homespun swing, and the home favorite with the championship pedigree.
But while the crowd pulled for Watson, a Kansas City native and honorary Prairie Dunes club member, Doyle found the shots when he needed them.
Doyle, who came from nine shots back to win last year, pulled ahead for good at the par-4 12th when he carded his first birdie since the third hole. He then twice defended a two-shot advantage with birdie putts.
At the par-4 14th, Watson rolled in a 40-foot birdie putt to briefly pull within one shot, but Doyle followed that up with an 8-footer for birdie.
The same happened at the 17th: Watson birdied, and Doyle responded with a backdoor 10-footer.
'Until the final putt is holes out, it isn't over,' said Doyle, who collected $470,000 for the win. 'That sticktuitiveness or whatever you want to call it, holds me in good stead.'
To the crowd's delight, Watson rolled in a 10-foot par putt on the 18th green to take second place alone.
During the first three rounds, Watson was 5 under par on the final five holes at Prairie Dunes. He went 1 under on those same holes Sunday, but it wasn't enough.
'It's very disappointing for me to play that way when the chips are down,' sighed Watson, who was especially unhappy with his 30 putts. 'I could have done a lot better for myself out there today, but it wasn't to be.'
Doyle, meanwhile, was a gracious champion, saying afterwards that the crowd's favoritism for Watson didn't bother him.
'He's a wonderful man, and why wouldn't Kansas be proud of him,' Doyle said.
Bruce Lietzke, the 2003 champion, fired a 4-under 66 and shared third place with Peter Jacobsen (69), the 2004 winner, at 5-under-par 275.
Scott Simpson and Andy Bean finished one shot further back following rounds of 68 and 69, respectively.
Loren Roberts, who set a record for the lowest score ever in a USGA Open championship with an eight-under 62 on Saturday, stumbled to a 73 on Sunday. He finished in a tie for eighth place at minus-2.