Marcus Mariota threw for 295 yards and four touchdowns in the rout. Five Titans scored a touchdown in the first half as Tennessee put together its best scoring performance this season with 35 points.
With the win, the Titans (5-5) also matched their five victories over the past two seasons combined.
DeMarco Murray set the tone on the opening play from scrimmage, running 75 yards for a touchdown. He finished with 123 yards and also threw a TD pass, becoming the first non-quarterback to do that for this franchise in the same game since Earl Campbell on Sept. 7, 1980, for the then-Houston Oilers.
Brian Orakpo had two of Tennessee's five sacks, and the Titans also forced three turnovers.
The Packers (4-5) started a three-game road swing by losing their third straight.