Smoking cigars during the round, the 53-year-old Mediate closed with a 5-under 66 - holing a 15-footer for par on the last at Jack Nicklaus-designed Harbor Shores - for a three-stroke victory over two-time defending champion Colin Montgomerie.
''I didn't know I shot 66,'' Mediate said. ''I didn't know what the heck I shot today. ... A lot of great things happened today and I don't believe I'm sitting here. I really don't.''
The bunker shot on 18 was the highlight of the day at the major championship.
''That was sick,'' Mediate said. ''As soon as it left the club, I knew it had a chance. Obviously, I didn't know it was going to make it, of course not, but I had a feeling I might. That made a big difference. It made a huge difference. Because Monty was there for three. At least three. And if I make bogey there, and it goes to one shot going to the last hole, who knows what happens? Who knows? So it was very fortunate at that time.''
Mediate finished at 19-under 265 to break the tournament record of 268 set by Sam Snead in 1973 at PGA National. The six-time PGA Tour winner became the first wire-to-wire winner in the event since Nicklaus in 1991 at PGA National.
Mediate matched the course and tournament records with an opening 62 and added rounds of 66 and 71 to take a two-stroke lead over Montgomerie into the final round.
''I won with the putter this week. Simple as that,'' Mediate said. ''I made a bunch of par putts that I had to make. Especially today. Especially early.''
Mediate broke through with the PGA Tour Champions major victory nearly eight years after losing the 2008 U.S. Open at Torrey Pines to Tiger Woods on the first extra hole after an 18-hole playoff. He thought that experience helped him Sunday.
''Absolutely. A hundred percent,'' Mediate said. ''Because going in there, it's like I played some of the best golf I ever played in my life that day and lost. OK. To the best player in the world at that time.
But today I'm playing against pretty much the other best player in the world of our age. Bernhard (Langer), obviously, too, but Colin, I mean, he doesn't make a whole bunch of mistakes.''
Mediate won for the third time on the 50-and-over tour, with the first two coming in 2013.
Montgomerie shot a 67 - and matched Snead for the second-best total in tournament history.
''I did nothing wrong. Did nothing wrong,'' Montgomerie said. ''Went out and shot 67. All credit to Rocco. He shot 66. And you can't knock it.''
The 52-year-old Scot won in 2014 at Harbor Shores and last year at French Lick in Indiana. He also won the 2014 U.S. Senior Open.
''All credit to Rocco,'' Montgomerie said. ''But I can hold my head high here and say I made great performance, 16-under par, 67, level 67s around here in the wind isn't all bad. I just got to congratulate Rocco and go home and come back again and see if we can win this again.''
Langer tied for third at 13 under in a failed bid to become the first player to win all five PGA Tour Champions majors. The 58-year-old German won the Regions Tradition last week in Alabama for his sixth senior major title and 100th worldwide victory. In Alabama, Langer joined Nicklaus as the only players to win four different senior majors.
Langer birdied the final two holes for a 67.
''There was a lot of good in my round today and even in the whole week,'' Langer said. ''It's just too many unforced errors.''
Brandt Jobe also was 13 under after a 68.
John DalCorobbo tied for seventh at 11 under to top the club professionals, shooting a 71. The 51-year-old DalCorobbo is a PGA assistant professional at Brickyard Crossing at Indianapolis Motor Speedway. He won the Senior PGA Professional in October to top the club pro qualifiers.