The Bills dominated the Titans in the second half, rolling to a 34-10 win. Buffalo is 5-2, and Tennessee 1-5.
DeAndre Hopkins spent the second half on the sideline, prompting speculation about his future with the team.
The Bills, who trailed 10-7 at halftime, outscored the Titans 27-0 in the second half and outgained them 299 to 72.
Josh Allen, who was 4-for-11 for 65 yards in the first half, was 21-of-33 for 323 yards and two touchdowns. Amari Cooper, who arrived in a trade with the Browns last week, caught his first pass with his new team for a 12-yard touchdown. He finished with four receptions for 66 yards.
Rookie Keon Coleman had his breakout game with four catches for 125 yards, and Ty Johnson caught a 4-yard touchdown. Khalil Shakir had seven receptions for 65 yards.
Ray Davis had a 16-yard touchdown run and led the Bills with 41 rushing yards on only five carries. James Cook had 12 carries for 32 yards and a touchdown.
Mason Rudolph, subbing for the injured Will Levis, completed 25 of 40 passes for the Titans for 215 yards with a touchdown and an interception. Tony Pollard had 16 carries for 61 yards.