The National Football League (NFL) has been playing games in Toronto, Ontario, Canada, since 1959 when an interleague game between the Chicago Cardinals of the NFL and the Toronto Argonauts (often shortened as Argos) of the Canadian Football League (CFL) took place at Exhibition Stadium. Subsequently, a number of neutral site preseason and regular season games between NFL teams have been staged in the city. Toronto is one of eight cities outside the United States, along with London, Mexico City, Frankfurt, São Paulo, Munich, Dublin, and Madrid, which have hosted regular season NFL games.

There have long been efforts to establish an NFL franchise in Toronto due to its market size. Toronto is among the largest cities in North America, and the largest in either Canada or the United States that is not home to an NFL team. The city hosts franchises in all of the other major professional sports leagues in the United States and Canada. As of 2020, the league has expressed interest in establishing a team in the city provided certain conditions are met, the most crucial being the construction of a new football-specific stadium.

The first professional U.S. football team to play a home game in Toronto was the Los Angeles Wildcats of the American Football League of 1926, the first major competitor to the National Football League for the dominance of professional football. While the Wildcats nominally represented Los Angeles, travel to the west coast posed a major obstacle at the time so the team was instead a traveling team based in Illinois. They played most of their games in the home stadiums of their opponents, with the exception of the Toronto game. The Wildcats lost the regular season game to the New York Yankees (which would join the NFL the following year) 28–0 in front of 10,000 fans at Maple Leaf Stadium on 8 November 1926. The game was relatively popular; at the time Canadian football still more closely resembled rugby football and would not adopt the forward pass until three years after the game.

In 1955, Eric Cradock, who would later become part owner of the Argos, stated that he was considering bringing two NFL teams to the city to play a game to test the market's interest in a full-time NFL franchise; this was four years after the second of two games, featuring the NFL's New York Giants, had been played in Ottawa against the local Canadian football team, the Ottawa Rough Riders. The NFL played its first game in Toronto in 1959, when the Toronto Argonauts of the Canadian Football League hosted the first of three NFL teams in a three-season span. The first ever appearance of an NFL team in Toronto was in August of that year during the Chicago Cardinals–Toronto Argonauts exhibition game, hosted to celebrate the grand opening of Exhibition Stadium; it broke the record for exhibition attendance in Canada at 27,770. These interleague exhibition games, which had been first tried in Ottawa in 1950 and were later staged in Montreal, were typically played by CFL rules in the first half and NFL rules in the second. The Argos lost all three games. The nearby Hamilton Tiger-Cats also hosted a game against the Bills, then an American Football League team. Buffalo lost the game 38–21, the only time a current or future NFL team would lose to a CFL team. In 1960 the New York Giants and Chicago Bears played an exhibition game at Varsity Stadium in the first game featuring two NFL teams to be played outside the United States.

During the 1982 NFL season the NFL players went on strike. In the absence of regular season NFL games, the National Football League Players Association scheduled a series of All-star games across the continent to raise funds. A game between the AFC East and NFC East was scheduled for Toronto's Varsity Stadium for October 24. However, the game was cancelled following a court ruling that permitted players who participated in the games to be sued by their clubs for violating their contracts.

A Toronto group had plans to bring the Buffalo Bills to Toronto to play an exhibition game at Exhibition Stadium in 1988, with hopes that it would become an annual event. However, following objections from CFL Commissioner Douglas Mitchell the game was vetoed by NFL Commissioner Pete Rozelle. The group would unsuccessfully continue to try to arrange a game for a future season. In 1993 the Cleveland Browns hosted one of their pre-season games in Toronto, which was organized by Molson Brewery, due to a scheduling conflict at Cleveland Stadium with the Cleveland Indians. As early as 1994 the Bills were considering hosting some of their regular season home games in Toronto, with SkyDome officials actively attempting to organize a regular season NFL game at the new stadium. When the NFL reached a five-year partnership agreement with the CFL in 1997, which included a $3 million loan to the Canadian league, the NFL received the CFL's blessing to hold an annual preseason or regular season game in either Toronto or Vancouver for the duration of the agreement. The Bills played in two pre-season American Bowls in Toronto in 1995 and 1997, organized by Paul Godfrey, in an attempt to prove the city's worthiness to host a franchise permanently. The Argos received $300,000 from the organizers to waive their exclusivity on football at the stadium for the game in 1995. In 2000 the NFL announced that SkyDome would host American Bowls in 2001 and 2003, but the games ultimately never took place, with the 2001 game being scrapped due to a lack of high-profile teams willing to participate. A planned game featuring the Chicago Bears in the 2002 season was called off in part due to the poor state of the artificial turf at the SkyDome.

At the 2005 Super Bowl, NFL Commissioner Paul Tagliabue said the league was considering staging an NFL regular season game in Toronto within a few years, with Godfrey and Rogers Communications bidding to host a game at the SkyDome, which had been renamed the Rogers Centre, in partnership with Maple Leaf Sports & Entertainment (MLSE) and Larry Tanenbaum, chairman and minority owner of MLSE. Toronto was one of five cities considered to host a game in 2007, but at the request of the CFL the NFL pushed back their plans for a game in the city by a year so as not to compete with the 95th Grey Cup being hosted in Toronto for the first time since 1992.

On October 18, 2007, the Bills announced that they were seeking NFL approval to play a pre-season and at least one regular season home game in Toronto in an attempt to regionalize the franchise and capitalize on the southern Ontario market. Moving games from Ralph Wilson Stadium required the approval of Erie County and the Empire State Development Corporation. For decades, the Bills have had a large fan base in southern Ontario. The team averages 15,000 Canadian fans a game, and has a Canadian sales office and radio affiliate in Toronto: CJCL. The NFL's television rules in Canada have been applied in a similar manner to secondary markets in the U.S., so that nearly all Bills games are televised in Toronto (on CFTO and CITY). Toronto is within a 75-mile (120 km) radius of Ralph Wilson Stadium, and thus it was subject to the league's blackout policy for home games that do not sell out.