With his victory at the Dover International Speedway, the "Monster Mile," Biffle became the first driver ever to capture the first two races in the Sprint Cup's season-ending "Race for the Chase," which decides the circuit's points champion.
He passed Roush Fencing teammate Matt Kenseth for the lead with eight laps to go and got the 14th win of his Sprint Cup career.
"I knew I had to race Matt, a great teammate, and Carl Edwards, but I couldn't give up," Biffle said in a post-race television interview. "The fans saw a great race."
Edwards, another Roush teammate, finished third, Mark Martin (Chevrolet) fourth, and two-time points champion Jimmy Johnson (Chevrolet) fifth.
Edwards leads both Biffle and Johnson by 10 points in the updated standings.
The third "Chase" race is next Sunday at Kansas City, Kan.