Jeff Demps rushed for 157 yards and two 10 victory on Saturday.
Chris Rainey gained 105 yards on the ground and John Brantley passed for 115 yards and a touchdown for the Gators (4-0, 2-0 SEC), who beat the Wildcats for the 25th straight time.
Morgan Newton threw for 124 yards, a touchdown and two interceptions for Kentucky (2-2, 0-1), which has dropped two in a row after opening the season with back-to-back wins.
Florida gained 405 yards on 46 carries by nine players, the sixth-best rushing performance in school history.
Behind Demps, Rainey and Mike Gillislee, who rushed for 84 yards, the Gators rushed for more yards than in any game since compiling 466 against New Mexico in 1989.
Their 25 consecutive victories over Kentucky ranks fourth all-time in the country among major conference opponents in a current series that is played annually.
"I was really pleased to get the win on the road. We had a lot of players that had never played a road game in the SEC," said Florida head coach Will Muschamp. "We're 4-0 and very pleased. We have a lot of things to work on but we are pleased with where we are."
The Wildcats haven't beaten the Gators since a 10-3 win in 1986 and they never sniffed an upset in this one, despite forcing Florida to punt on its first two possessions.
"For five minutes in the game we looked like a pretty good football team, and then the things that we had been doing in the past started showing up -- turnovers, giving short fields," said Kentucky head coach Joker Phillips.
Florida built a 21-3 lead in the first quarter. A fumble by Kentucky's Josh Clemons led to Brantley's 45-yard touchdown pass to Gerald Christian and the Gators upped the lead to 14-0 on Demps' 20-yard run on their next possession.
Matt Elam then intercepted Newton, returning it 18 yards to the Kentucky 28, and Rainey's 27-yard run set up a one-yard TD run by Trey Burton. The Wildcats responded with a 24-yard field goal from Craig McIntosh to pull within 21-3.
But the Gators kept their foot on the pedal, taking a 28-3 lead early in the second when defensive tackle Jaye Howard recovered Newton's fumble near the goal line for a touchdown.
Caleb Sturgis kicked a 45-yard field goal for a 31-3 lead before Kentucky turned a fumble into Newton's 19-yard touchdown pass to La'Rod King with 1:18 left in the first half.
They were the last Wildcat points.
Demps scored on an 84-yard run in the third quarter and Sturgis kicked a 27- yard field goal later in the frame that was set up by a Newton interception. Gillislee broke off a 60-yard touchdown run in the fourth quarter for the final score.
The Gators have outscored their first four opponents of the season 161-36.
Florida's 25-game winning streak over Kentucky is topped only by Notre Dame's 43-game streak over Navy (1964-2006), Nebraska's 36-gamer against Kansas (1969-2004) and Tennessee's current 26-game streak over Kentucky, which dates to 1985. The Gators lead the all-time series with Kentucky 45-17.