Lewis signed a four-year, $19.8 million contract in 2018 and was set to hold a $5.1 million cap number in 2020. Wake signed a three-year, $23 million contract in 2019 and was set to hold a cap figure of $8.6 million in 2020.
The Titans save $4 million by letting Lewis go and $5.6 million with the release of Wake.
Lewis, 29, and Wake, 38, will now be free to sign with other teams.
Lewis rushed for 209 yards in 16 games last season, making one start. In two seasons with the Titans, Lewis had 209 carries for 726 yards and a touchdown. Lewis also posted 84 receptions for 564 yards and two touchdowns.
Tennessee used Lewis primarily as a third-down specialist in a receiving role out of the backfield. According to ESPN Stats & Info, Lewis played 150 snaps (80%) on third downs last season while starter Derrick Henry played on only 24 (13%) of the third downs.
Wake played in nine games for the Titans last season, and he finished with five tackles and 2.5 sacks. The veteran linebacker finished last season on injured reserve.
He spent his first 10 NFL seasons with the Dolphins before signing with the Titans. Wake has posted 364 tackles and 100.5 sacks in 11 seasons.
Lewis' departure frees up salary room for the Titans to re-sign Henry, who is set to become a free agent after he led the NFL with 1,540 rushing yards and tied for the league lead with 16 rushing touchdowns. There's a possibility that Tennessee could place the franchise tag on Henry.
Releasing Wake could lead to the Titans adding a veteran pass-rusher in free agency. The team also could possibly address the position via the draft.
The Titans also could use the freed-up money to try to re-sign quarterback Ryan Tannehill to a long-term contract.
In another move, the Titans re-signed defensive back and special-teams player Chris Milton to a one-year contract. Milton tied for sixth on the team with five special-teams tackles in 2019 while playing in six games.