It began on Thursday, September 10, 2015, with the annual kickoff game featuring the defending Super Bowl XLIX champion New England Patriots defeating the Pittsburgh Steelers.

The season concluded with Super Bowl 50, the league's championship game, on Sunday, February 7, 2016, at Levi's Stadium in Santa Clara, California,[2] with the Denver Broncos defeating the Carolina Panthers 24–10.

During the 2015 season, the Oakland Raiders, the St. Louis Rams, and the San Diego Chargers announced their intentions to relocate back to Los Angeles in the ensuing off-season (all three teams had previously resided in the city at various points in their history).

These players were wide receivers Dez Bryant (Cowboys)[32] and Demaryius Thomas (Broncos),[33] linebacker Justin Houston (Chiefs),[34] and defensive end Jason Pierre-Paul (Giants).

The Detroit Lions acquired All-Pro defensive tackle Haloti Ngata from the Baltimore Ravens in exchange for draft picks to help make up for the loss of Ndamukong Suh in free agency.

[42] The draft process began with the NFL Scouting Combine, where draft-eligible players were evaluated by team personnel, which was held in Indianapolis on February 17–23.

Bednarik was selected as a member of the NFL's 75th Anniversary All-Time Two-Way Team and was inducted into the Pro Football Hall of Fame in his first year of eligibility in 1967.

Immediately upon the announcement of the appeal verdict, the league filed suit against the NFL Players Association in civil court in an effort to gain a ruling upholding the punishment.

[83] Judge Richard M. Berman pushed the two sides hard to reach a settlement, but when they were unable to he ruled for Brady and the union vacating the suspension imposed by the league.

[84][85] The two Patriots employees, assistant equipment manager John Jastremski and officials locker room attendant Jim McNally, who had previously been suspended by the team were allowed by the league to be reinstated in September.

The San Francisco 49ers lost three potential starters as linebackers Patrick Willis and Chris Borland and offensive tackle Anthony Davis all announced their retirements.

[100] The league stripped the Atlanta Falcons of their selection in the fifth round of the 2016 draft after it was determined that they had been using pre-recorded crowd noise during the team's home games throughout 2013 and into 2014.

In addition to losing the draft pick the franchise was fined $350,000 and team president Rich McKay was suspended from his post as chairman of the league's Competition Committee for three months starting in April.

[108] The 5th NFL Honors, saluting the best players and plays from 2015 season, was held at the Bill Graham Civic Auditorium in San Francisco, California on February 6, 2016.

The decision to convert was made 5 days later, and the turf field was installed in time for the Texans next home game against Tampa Bay in Week 3.

[260] On February 19, 2015, the Oakland Raiders and San Diego Chargers announced plans for a privately financed $1.7 billion stadium that the two teams would build in Carson, California, if they were to move to the Los Angeles market.

[261] Such a move would have marked a return to the nation's second-largest market for both teams; the Raiders played in Los Angeles from 1982 to 1994 while the Chargers called LA home for their inaugural season in the American Football League.

The Chargers had been looking to replace Qualcomm Stadium (which, like the O.co Coliseum opened in the late 1960s) since at least 2003, and had an annual out clause in which it could move in exchange for paying a fine to the city of San Diego for its remaining years on its lease.

The City of St. Louis, in subsequent years, made changes to the scoreboard and increased the natural lighting by replacing panels with windows, although the overall feel remained dark.

Publicly, city, county and state officials expressed no interest in providing further funding to the Edward Jones Dome in light of those entities, as well as taxpayers, continuing to owe approximately $300 million more on that facility.

In lieu of this the city of St. Louis responded on January 9, 2015, by unveiling an outdoor, open-air, riverfront stadium that could accommodate the Rams and an MLS team with the hopes that the NFL bylaws would force them to stay.

[267] Farmers Field was a proposal from Anschutz Entertainment Group to lure an NFL team to Los Angeles by promising a new stadium, but AEG placed restrictions on any relocation that the rest of the league found unacceptable, and the project had lain dormant since 2012.

Gold footballs were given to each high school that has had a player or coach appear in the Super Bowl, and "homecoming" events were held by teams at games.

On September 22, Sports Business Daily reported that NFL VP/Communications Brian McCarthy stated it was because the Oakland Athletics were still playing at the O.co Coliseum (the only stadium that is still shared by both an NFL team and a Major League Baseball team, which forces the Raiders to play on its dirt infield until the baseball season concludes), but the Coliseum's General Manager Chris Wright responded by saying that the Raiders told him not to apply the gold marks for the remaining regular season games.

The other four teams involved (Buffalo Bills, Jacksonville Jaguars, New York Jets, and Tampa Bay Buccaneers) wore all-new uniforms for the games.

[292] On March 23, 2015, league owners voted to, as an experiment, suspend the NFL's blackout rules for the 2015 season; no games were blacked out in their home markets because of insufficient ticket sales.

These moves came after the Federal Communications Commission's September 2014 decision to stop enforcing blackout rules on terrestrial television stations, and the fact that, ultimately, no games were blacked out at all during the 2014 season.

[294] The game only aired on television in the team's home markets (in accordance with NFL policies), as well as in the United Kingdom on BBC Two and Sky Sports, and in China.

[295] Brian Rolapp, the league's executive vice president of media, explained that the experiment was part of the NFL's efforts to attempt alternative distribution models for games, such as those that would appeal to viewers who do not subscribe to pay television.

[297] The NFL entered into a social media partnership with Snapchat to present live stories with behind-the-scenes and fan perspectives from selected games.