Wyndham Clark, Brian Harman and Xander Schauffele all finished a shot behind Scheffler, with Clark going agonizingly close to forcing a playoff with Scheffler.
All three of the challengers in the all-American battle needed birdies on the 18th and Clark was distraught after his 17-foot birdie putt lipped out.
That left Scheffler, waiting on the range at 20-under, to celebrate his historic achievement of consecutive wins at the Ponte Vedra Beach course as he followed up his victory at Bay Hill last week with another display of his consistency.
Scheffler entered the final round trailing overnight leader Schauffele by five shots but got his charge under way with an eagle on the par-4 fourth, where he holed out from 92 yards, before making three more birdies before the turn.
It was classic Scheffler on the back nine as he kept out of trouble and added three more birdies for his bogey-free 64.
Then it was over to the trio chasing him to make up the gap and while Clark made birdies on 16 and 17, he fell just short on the last.
"We had a great finish yesterday and then got off to a slow start today but then the hole out on four kind of propelled us a little bit," said Scheffler.
"I hit a lot of good shots, did a lot of good things this week and it's nice to come out on top.
"It's tough enough to win one Players and so to have it back-to-back is extremely special."
The chasing trio paid the price for crucial bogeys.
Schauffele made bogeys on 14 and 15 and reigning US Open winner Clark's bid looked to have faded after bogeys on 10 and 14.
'Gutted'
Clark, who won this season at Pebble Beach, had his worst putting round of the week but found his touch with birdies on 16 and 17 before the 18th ended in frustration.
"I don't know how that putt doesn't go in," he said. "It was kind of right centre with like a foot to go, and I knew it was going to keep breaking, but it had speed and I thought it was going to good inside left, and even when it kind of lipped, I thought it would lip in.
"I'm pretty gutted it didn't go in."
"You finish second, you get a bunch of points and money and all that stuff, but it just sucks.
"I've always wanted and dreamed about making a putt that really mattered to either force a playoff or win a tournament, and I have yet to do it in my professional career, so I was pretty bummed that I didn't have one of those really awesome moments.
"I'm still a little beside myself. I'm still shocked that putt didn't go in."
Harman was able to be more philosophical about his loss after recovering from a bogey on the sixth to make four birdies in the next five holes, his 68 not quite enough to catch Scheffler.
"He's the best player in the world, and this is a championship golf course, and so - as far as if you look at it on paper, the best player this week won," Harman said.
"That's kind of what you want in a golf tournament. We all had our chances, and he just performed - he out-executed two or three more times than the rest of us."
Schauffele, who saw his overnight lead vanish, had chances down the stretch and he was left to rue a missed seven-foot birdie putt on the 17th as he shot 70.
"If I made that, it could have been a different story. I hung tough but no surprise to see Scottie's name up there," he said.
England's Matt Fitzpatrick was fifth, four shots off the lead, after ending his round of 69 with four straight birdies.
South Korea's Kim Si Woo, the youngest Players winner from 2017, shared sixth, five strokes adrift alongside Japan's Hideki Matsuyama, the 2021 Masters winner.