The season began on September 5, 2019, with the NFL Kickoff Game, in which the Green Bay Packers defeated the Chicago Bears.

The season concluded with Super Bowl LIV, the league's championship game, on February 2, 2020, at Hard Rock Stadium in Miami, Florida, in which the American Football Conference (AFC) champion Kansas City Chiefs defeated the National Football Conference (NFC) champion San Francisco 49ers, to win their second Super Bowl championship.

On March 8, teams were allowed to exercise 2019 options for players with option clauses in their contracts, to submit qualifying offers to their pending restricted free agents and to submit minimum salary tenders to retain exclusive negotiating rights to their players with expiring 2018 contracts who had fewer than three accrued seasons of free-agent credit.

[88] In June 2019, the league clarified March 2019 temporary rule change regarding reviews of pass interference plays as follows:[89] Training camps for the 2019 season were held in late July through August.

[100][101] On August 17, Dallas and the Los Angeles Rams played a preseason game at Aloha Stadium in Honolulu, Hawaii, the former home of the Pro Bowl.

[105] Thirty-three Packers players refused to play on the surface, including starting quarterback Aaron Rodgers.

[107][108] The Chicago Bears (who, as the Decatur Staleys, were one of the 14 charter members of the league) celebrated their centennial season with commemorative events throughout 2019.

[110] The NFL aired a special two-minute commercial during Super Bowl LIII to launch the centennial campaign, which featured a gala dinner attended by 40 current and former NFL players, including Los Angeles Rams RB Todd Gurley, then-New York Giants WR Odell Beckham Jr., New England QB Tom Brady, former Indianapolis and Denver QB Peyton Manning, Hall of Fame WRs Jerry Rice and Michael Irvin, and Hall of Fame QB Terry Bradshaw,[111] NFL commissioner Roger Goodell (who delivered the welcome address), NFL officials Ron Torbert and Sarah Thomas, viral teenage girl football star Samantha Gordon,[112] and video game streamer Tyler "Ninja" Blevins.

[113] In honor of the site of the first NFL game, the league announced plans to donate a new artificial turf field to Triangle Park in Dayton, Ohio, home field of the former Dayton Triangles, intending for Cincinnati to hold a day of training camp at the site.

However, the project was rejected by the city after concerns that construction could potentially disturb a Native American burial site.

During his post-game press conference, Luck stated that his retirement was due to the recent mental and physical difficulties of playing football.

[136] Brown was held out by his former team, the Pittsburgh Steelers during week 17 of 2018 due to a heated falling out with quarterback Ben Roethlisberger.

Brown then accepted the new helmet model and returned to practice, but later wore inadequate footwear in a cryogenic chamber and got frostbite on his feet, causing additional concern for his availability in Week 1.

On September 10, allegations that Brown had raped his former trainer, Britney Taylor, caused speculation that he might be put on the commissioner's exempt list, barring him from playing.

[140] In the final seconds of a November 14 Thursday Night Football matchup between the Pittsburgh Steelers and Cleveland Browns, Browns defensive end Myles Garrett tackled Steelers quarterback Mason Rudolph after Rudolph completed a screen pass to running back Trey Edmunds.

Following the game, Garrett was suspended for the remainder of 2019 and required to apply for reinstatement in 2020, while Pouncey and Ogunjobi received 2-game and 1-game suspensions, respectively.

[145] This was the second time the current Patriots administration was involved in an unauthorized videotaping scandal, following the Spygate controversy in 2007.

[223] Fangio, a first-time head coach with over 30 years experience as an assistant dating back to the USFL, most recently as defensive coordinator of the Chicago Bears, was hired on January 10, 2019.

[229] Gase, who was previously the head coach of the Miami Dolphins, posting a 23–25 (.479) record in three seasons, was hired on January 11, 2019.

He was previously the head coach for the Arizona Cardinals for five seasons with 50–32–1 (.608) record from 2013 to 2017, leading them to an NFC Championship Game appearance in 2015.

If the Bills chose not to exercise the buyout window, they will not be allowed to relocate until after the 2022 season, when the current lease expires.

In December 2018, the city of Oakland filed a lawsuit against the Raiders and the NFL seeking financial damages and unpaid debt, claiming the relocation was illegal but not asking for an injunction forcing the team to stay.

The Raiders stated that if any legal action was filed against them, that they would not renew with the Coliseum and find another, undetermined, temporary home for 2019 until Allegiant Stadium was finished.

[250] With the 49ers refusing to waive territorial rights, the Raiders were forced to either renegotiate with the Coliseum[251] or find a temporary stadium outside the San Francisco Bay Area (something that the Raiders management was reluctant to do, though the team acknowledged and considered bids from San Antonio, Texas, and Tucson, Arizona).

This includes "cross-flexing" (switching) Sunday afternoon games between CBS and Fox before or during the season (regardless of the conference of the visiting team).

Fox airs Thursday Night Football along with NFL Network, with Amazon Video and Twitch continuing to simulcast those games online in the second and final year of the two sites' current contract.

It was originally reported that all media markets in the U.S. who have CBS and Fox affiliates will have access to three Sunday afternoon games every week regardless of whether the local team is playing at home.

[270] Witten was not replaced; Booger McFarland, who spent the previous season commentating from atop a crane-like contraption on the sideline, was moved into the booth.

[272] Twitch added "co-streaming" with live commentary from specially chosen users of the service for its 2019 Thursday night games.