The deal worth $94 million has $66 million in guarantees, including a $24 million signing bonus, sources said.
"We are not done yet," Simmons said on Twitter. "We have so much work to do!"
The deal provides long-term security for Simmons, who had been set to play on the fifth-year option at $10.75 million. Titans general manager Ran Carthon prioritized signing Simmons to the extension when he came to Tennessee in January.
Simmons posted 7.5 sacks last season despite playing the last eight games with an injured ankle. The 25-year-old made his second Pro Bowl last season. He is a two-time second-team All-Pro.
The Titans selected Simmons with the No. 19 overall pick in 2019 draft. Simmons has 21 sacks, 28 tackles for a loss and 46 quarterback hits in four seasons with the Titans.