[9][10] In his first NFL game in the regular season against the Pittsburgh Steelers, Wolfe came out with 3 tackles and a sack for a loss of 9 yards.

In a preseason game against the Seattle Seahawks, Wolfe suffered a spinal cord injury and was carted off the field.

Without Wolfe, the Broncos reached Super Bowl XLVIII where they lost to the Seattle Seahawks.

After serving a four-game suspension for a PED violation,[11] Wolfe returned to establish himself as one of the best-run stuffers in the game, which eventually led to him being named AFC Defensive Player of the Week after the Broncos defense completely neutralized the undefeated Green Bay Packers offense in Week 8.

The Broncos finished the 2016 season with a 9–7 record and missed the playoffs for the first time in Wolfe's career.

[22] However, on November 15, 2021, head coach John Harbaugh said that Wolfe was expected to be out for the rest of the season.

[23] On June 14, 2022, Wolfe and the Ravens came to terms on an injury settlement leading to his release from the team.

[26] Source:[27] On October 3, 2022, Wolfe joined 104.3 The Fan in Denver as a sports-talk radio host on the station's marquee show, "The Drive.