The Todd Pletcher-trained colt covered 1e miles in 1:47.49 with John Velazquez aboard, breaking the mark of 1:47.72 he set last year when winning the Florida Derby.
Quality Road, a 4-year-old who was named the 2009 Aiken-trained Horse of the Year by the Aiken Thoroughbred Racing Hall of Fame and Museum, was broken and trained in Aiken by Legacy Stable's Ron Stevens.
Dry Martini was second, a length in front of Delightful Kiss in third.
Quality Road paid $2.80, $2.40 and $2.10, Dry Martini earned $6.20 and $4.20, and Delightful Kiss returned $4.80.
Quality Road's margin of victory was the largest in the Donn's 52 runnings, breaking the record of nine lengths set in 1972 by Going Straight.
"There's not too much you can say about a performance like that," Pletcher said. "He showed up, ran one of his best races, and you couldn't be much more impressed than that."
Quality Road joined Harlan's Holiday (2002-03) and Cryptoclearance (1987, '89) as the only horses to win the Florida Derby and return as an older horse to win the Donn.
WHIRLAWAY STAKES: In New York, Peppi Knows won the $100,000 event at chilly Aqueduct Racetrack after favorite Eightyfiveinafifty bolted through the outside rail on the first turn and unseated jockey Jorge Chavez.
The frightening spill resulted in Chavez being taken to a hospital complaining of soreness and Eightyfiveinafifty being caught in the barn area suffering from a 2-inch cut to his right hind leg.
"He'll need a couple of stitches, I'll need a Valium," Eightyfiveinafafty's trainer Gary Contessa said. "I'm completely mystified as to what happened."
Chavez was conscious and walking around before leaving for the hospital, New York Racing Association officials said.
Eightyfiveinafifty was dueling for the lead along the inside rail at the start, then suddenly swung to the far outside. Coming out of the first turn, the colt ran through a temporary railing, then another rail as Chavez fell hard on the dirt track.
Contessa said his colt's bit was broken and the rein was shredded, but he wasn't sure whether it happened during the race or after Eightyfiveinafifty bolted.
WASHED OUT: In Arcadia, Calif., racing was canceled at Santa Anita because of heavy rain that left the synthetic surface unsuitable.