The All-Stars played from 1915 to 1917 under the leadership of Eugene F. Dooley; in 1917, Dooley, along with his star player Barney Lepper, took the team on a barnstorming tour of midwestern pro football teams. In 1918, the city's teams were not allowed to play outside the area because of the 1918 flu pandemic; Dooley and Lepper discontinued the All-Stars. Shoe salesman Warren D. Patterson, at the same time as this, formed a new team known as the Buffalo Niagaras, signing former Youngstown Patricians quarterback Ernest "Tommy" Hughitt as his quarterback. As the Niagaras, the team won a citywide championship in 1918, going undefeated with a 6–0–0 record (including a forfeit), having only one touchdown scored on them in any of their six games. They were one of the few upper-level teams still able to play games that year, with most of the top level teams (such as the Patricians, Canton Bulldogs and Massillon Tigers) all having suspended operations due to the pandemic and/or World War I player shortages; this allowed Buffalo to get a leg up on its Ohio competition and sign otherwise-unemployed players, setting a course for bringing the region on par with the Ohio League and the ultimate establishment of the NFL. With that, they could have theoretically staked a claim to being the best team in the nation, especially considering how the team would perform over the next three seasons, but the Professional Football Researchers Association is dismissive of any claim that does not come from the Ohio League, and gives the mythical "national title" to the Dayton Triangles, who also went undefeated that year. When the New York Pro Football League reopened in 1919, the team, now reorganized into a franchise known as the Prospects, defeated the Rochester Jeffersons for the league title in a two-game Thanksgiving weekend tournament. The two teams tied the Thanksgiving Day game, but Buffalo handily defeated Rochester 20–0 the following Sunday.
Lepper teamed up with Hughitt and Patterson in early 1920 to create the Buffalo All-Americans, then quickly sold the team to Frank McNeil, a somewhat abrasive and aggressive owner who was able to get the team into the National Football League for its first season. However records indicate he may not have actually entered his team into the American Professional Football Association until 1921, the All-Americans are generally shown as the third-place team in league standings from that year (the confusion stems from a statement in the minutes from the league's April 1921 reorganization meeting admitting an unidentified team from Buffalo; this may have instead been the Tonawanda Kardex, who joined the league in 1921, playing only one game). Patterson held on to the Prospects name and put together a lower quality team that played through 1923, including a 1922 game against the All-Americans themselves.
The All-Americans had success during its first couple of APFA seasons, posting a 9–1–1 regular season record in 1920, becoming the first professional NFL team to win by margins of 20 or more points in each of its first four games, an asterisked record which was not tied until the 2007 New England Patriots' offense duplicated the feat; the asterisk is because, in the early NFL, the All-Americans played five of its 11 games against non-league opponents.
Unique for a professional football team, the All-Americans had a sharing agreement with the Union Club of Phoenixville, a side project managed by All-Americans player Heinie Miller. Miller would take himself and seven other All-Americans to Phoenixville, Pennsylvania to play games on Saturdays (Pennsylvania had blue laws that prevented play on Sunday), and then return to Buffalo on Sundays. This sharing agreement lasted into 1921 when Miller formed the new Union Quakers of Philadelphia, but All-Americans owner Frank McNeil put a halt to the agreement halfway through the 1921 season after the Quakers played the Canton Bulldogs and wore out the All-Americans players. Five All-Americans left the team to play for the Quakers full-time; Buffalo had the pickings of the then-defunct Detroit Tigers to replenish their roster.
In 1920, the Akron Pros held the All-Americans to a scoreless tie in front of only 3,000 fans. At the game, Akron owners Frank Nied and Art Ranney agreed to sell Bob Nash to Buffalo for $300 and five per cent of the gate, in the first known player deal between NFL clubs.
Along with the Decatur Staleys and Akron Pros, Buffalo claimed a share of the 1920 league title. That same season the Pros held the best record in the league, and only had to avoid losing a game. Meanwhile, Buffalo and the Staleys had to win in order to capture the AFPA Championship. The Pros were able to hold the Staleys to a scoreless tie at Cub Park. However, the Pros still had to play the All-Americans who were fresh from a 7–3 win over the Canton Bulldogs at New York City's Polo Grounds. Despite Buffalo's confidence going into the match, the Pros also held the All-Americans to scoreless tie.
Both the All-Americans and the Staleys complained about the championship, arguing that Akron had only tied, but not defeated them. However, Joseph Carr (then serving only as owner of his Columbus Panhandles team) moved at the league's meeting in April 1921 to give Akron the sole title and the rights to the Brunswick-Balke Collender Cup. The motion was accepted, and Buffalo finished in third place, with Chicago in second place. The only loss Buffalo had was against the Canton Bulldogs in 1920. According to modern NFL tie-breaking rules, the 1920 Buffalo All-Americans would be co-champions. They would be tied with the Akron Pros in win percentage, 9 1⁄2 losses (.864), both teams beating out the Decatur Staleys, who would have a season that counted 11 wins to 2 losses (.846).
On November 27, 1921, the All-Americans claimed the AFPA title with a record of 9–0–2. However, for reason still unknown, owner Frank McNeil agreed to play two more games. He did tell the Buffalo media that the two games were exhibitions and would have no bearing on the team's claim to the AFPA title. George Halas and the Chicago Staleys manage to capture second place in the AFPA in 1921, with their only loss of the season against Buffalo. McNeil scheduled the two additional games against the Pros and Staleys back-to-back. The first game was scheduled for December 3 against the tough Pros, after which his team would take an all-night train to Chicago to play the Staleys the next day.
The All-Americans defeated the Pros, arriving in Chicago worn out and in no condition to play the Staleys, and lost. McNeil still believed his team was the AFPA's 1921 champion, and even invested in tiny gold footballs for his players to commemorate the achievement. However Halas declared that the title was Chicago's, basing his claim on his belief that the second game of the Buffalo-Chicago series mattered more than the first. He also pointed out that the aggregate score of the two games was 16–14 in favor of the Staleys. McNeil insisted the Buffalo All-Americans were the champions, still maintaining that the last two games his team played were merely exhibitions. It didn't matter. The league awarded the championship by a vote of the Association's executive committee in January 1922 to the Staleys.
This episode is referred to by several sports historians and Buffalo sports fans as the "Staley Swindle." McNeil eventually went to his grave trying to get the league's decision overturned. In their decision, based on a generally accepted (but now obsolete) rule that if two teams play each other more than once in a season, the second game counts more than the first, the executive committee followed established tradition. Had Buffalo not played the last game, they would have had an undefeated season and won the title.
Under the leadership of player-coach Tommy Hughitt, the All-Americans, though they never equaled the success of the first two seasons, continued to post winning records in 1922 and 1923. Star running back Ockie Anderson's knees deteriorated during the 1922 season, forcing his early retirement and beginning the team's decline. In 1924, owner Frank McNeil sold the team back to Hughitt and Warren D. Patterson, who immediately changed the team name to Bisons (a stock name for Buffalo sports teams) and signed several players (Pete Calac, Benny Boynton and Jim Ailinger being among them) to make another run at the title. After starting the season 6–2, the team lost their last three to once again end up marginally above .500. Hughitt retired at the end of the season. After Hughitt's retirement at the end of the 1924 season, the team struggled for the rest of its lifespan.
Jim Kendrick announced his "Buffalo Rangers" experiment, fielding an exhibition team of players from Texas and the Southwestern United States for the 1926 season. His plan was that this exhibition squad would then represent Buffalo in the NFL. Because most of the players were Texans, the team was nicknamed the "Rangers" in deference to the state's legendary peacekeeping force. Along with the West Coast's Los Angeles Buccaneers and the South's Louisville Colonels, it was one of three teams that represented cities outside the NFL's existing footprint. The Buffalo media alternately referred to the team as the "Bison Rangers," combining the old name with the new so that fans might more easily identify with the team that was on its third name in seven years. The one-year experiment brought a 4–4–2 (.500) season. Buffalo expected Kendrick to return to field the Rangers for the 1927 season, however he signed with the New York Giants, and most of the remaining players went their separate ways, citing their dislike for Buffalo's cold winters as the primary reason for leaving.1927 season. After five games (all losses, all but one being a shutout), the team suspended operations and failed to finish the season. The team did not return to play in 1928, but returned in 1929 with former Oorang Indian Al Jolley as coach. Among their players that year was Jess Rodriguez, the first Hispanic-American player in the NFL (the Frankford Yellow Jackets had hired Ignacio "Lou" Molinet two years prior, but Molinet was a Cuban national). Much like in 1927, the Bisons failed to win a game until their final game, when in a case of cosmic irony they upset the Chicago Bears 19–7; thus, the very team that had spoiled their undefeated season in 1921 saved them from the indignity of a winless season in 1929. With the Great Depression underway, the Bisons folded, never to return again. During the season, the Bisons set an NFL record of six consecutive games without ever having a lead in regulation play. The record was tied in 2012 by the Kansas City Chiefs.
At least one further game against an NFL team was played in Buffalo in the wake of the Bisons' failure: the independent Buffalo Bears narrowly lost, 8–6, to the Cleveland Indians in a 1931 contest. Buffalo would become a regular "neutral site" for NFL exhibitions from 1938 to 1958. The team has no official relation to future Buffalo pro football franchises: the Buffalo Indians and Tigers of the third American Football League, the Buffalo Bisons of the AAFC, or the Buffalo Bills of today which was one of the new AFL teams (formation announced in 1959) that first played in 1960.