He broke the 54-hole tournament record shared by Woods (1997) and Floyd (1976) on yesterday, having set a 36-hole record a day earlier.
Spieth, the reigning Australian Open champion, showed composure way beyond his years becoming only the fifth wire-to-wire winner, joining Craig Wood in 1941, Arnold Palmer in 1960, Jack Nicklaus in 1972 and Raymond Floyd in 1976.
"It's the most incredible week of my life," said Spieth. "It's a dream come true. I'm still kind of in shock a little bit."
He added: "It was very nerve-wracking today. With two major champions right behind me, I couldn't let up."
Rose got within three shots a few times on the front nine while Mickelson was within four on the front nine, but neither could make further inroads.
Spieth's 28 birdies eclipsed the most in a single Masters tournament, taking over from Mickelson's 25 in 2001 and came just a year after finishing as runner-up to Bubba Watson on debut.
McIlroy closed with a 66 to finish at 12-under in fourth as he chased the career grand slam.
He was one clear of 23-year-old Japanese young gun Hideki Matsuyama who also shot 66.
Woods could only muster a 73 yesterday, leaving the 14-time major winner in a tie for 17th.
Australia had its worst Masters performance since 2001, with Jason Day leading the way at one-under-287 in a tie for 28th.
Day dropped a disappointing 75 on Sunday but still bested 2013 champion Adam Scott who posted a 74 to finish one-over, thanks mainly to a quadruple-bogey seven on the picturesque par-three 12th when he found water twice.
"Overall a pretty disappointing week, really," Day said.
- AAP
