The deal will pay Dupree more than $16 million per year.
Dupree gives the Titans' defense a much-needed presence off the edge. He also is capable of being a down lineman in nickel packages.
The Titans fielded only three outside linebackers for most of their games last season, which resulted in Harold Landry playing 94% of the snaps.
Tennessee hasn't had a pass-rusher register 10 sacks in a season since Brian Orakpo finished with 10.5 in 2017.
After hitting his stride with 11.5 sacks for the Pittsburgh Steelers during the 2019 season, Dupree, who turned 28 in February, was on track for another strong season in 2020 before suffering a torn ACL in Week 12 against the Baltimore Ravens.
He told Fowler earlier this month he planned to be a full participant in an NFL training camp based on positive feedback from his doctors.
Playing on the franchise tag after the two sides were unable to work out a long-term deal, Dupree had 8 sacks, 31 combined tackles, 8 tackles for loss and 15 quarterback hits for Pittsburgh last season.
The 2019 campaign was his healthiest since being taken by the Steelers out of Kentucky in the first round of the 2015 NFL draft; forming a fierce tandem with T.J. Watt, Dupree recorded 17 quarterback hits and had 16 tackles for loss.
Not only was Dupree a foundational piece for the Steelers' stout defense, he was a glue guy, bonding the locker room with his upbeat attitude and personality. He finished his Steelers career with 66 starts, 39.5 sacks, 169 solo tackles, 54 tackles for loss, an interception return for a touchdown and 65 quarterback hits.
ESPN's Brooke Pryor and Turron Davenport contributed to this report.