The contract is the richest deal for an offensive lineman in NFL history. Lewan's deal is the highest in terms of average annual value ($16 million) and guarantees.
The Titans announced the extension Friday but did not disclose terms.
Lewan, 27, reported to camp this week after sitting out the team's mandatory minicamp in June in hopes of landing a new contract.
Titans general manager Jon Robinson said earlier this week that he had "really good discussions" with Lewan's reps and believed the two sides were "headed in the right direction" in terms of an extension.
Lewan and his representatives were aiming to surpass New York Giants left tackle Nate Solder as the NFL's highest-paid offensive lineman. Solder received a four-year, $62 million deal with $35 million guaranteed from the Giants in March. Before Friday, the Washington Redskins' Trent Williams had the highest amount of guarantees ($41.3 million) in the contract that he signed in 2015.
Lewan, selected 11th overall by the Titans in the 2014 draft, has been a Pro Bowl selection for the past two seasons.
ESPN's Cameron Wolfe and ESPN Stats & Information contributed to this report.