The win was Leffler's second Busch victory and the first checkered flag for Toyota.
Aric Almirola led the 43-car field for much of the contest but fell back during a pit stop on lap 95.
Leffler moved into second place with 13 laps to go and took advantage of a caution flag with nine laps left to pass Biffle on the restart. He held Biffle off the rest of the way to grab the win.
Jordana Brewster on Paul Walker: 'He was an enormous presence in my life'
Couple mistakenly served bag of cash at McDonald's drive-thru