The Panthers competed in the first American Football League (AFL), founded by Charles "Cash and Carry" Pyle (1882–1939), in 1926. The Panthers, owned by General Charles X. Zimmerman (1865–1926) (the vice president of the AFL), played their home games in old Luna Bowl in Luna Park. Coached by Ray E. Watts, the team drew its players from Ohio colleges and universities and raided the rosters of early National Football League (NFL) teams based in Ohio
The veteran squad led by tailback Al Michaels was one of only two AFL franchises (the other was the New York Yankees) to average more than 12 points per game. Other former Cleveland Bulldogs Dave Noble and Doc Elliott helped provide offensive firepower, while two-sport star Cookie Cunningham excelled at end, scoring twice on long passes in an October 3, 1926, game against the Los Angeles Wildcats.
In terms of fan support, the Panthers appeared to have had a good start, defeating the Yankees in their first game, at Luna Bowl in front of a reported 22,000 people, but after a second home victory (17-13, against the Wildcats) in which the attendance figures were apparently not reported, and a third straight home win (this time 23-7 against the Rock Island Independents) in front of only 7000 people, it was becoming evident that the Panthers were in trouble despite being in first place with an undefeated record. A 19-12 defeat in front of only 3000 spectators in Chicago's baseball Comiskey Park (the stadium of the Chicago White Sox), foreshadowed the inevitable as the similarly-troubled Newark Bears withdrew from the league on October 24, 1926.
The next week, the Panthers returned home to old Luna Park for a rematch with the Los Angeles Wildcats, a hard-fought game dominated by defense, with Cleveland guard Al Nesser dictating much of the game until a fourth quarter fumble by Al Michaels led to the only score of the game in a 6-0 Wildcats win. While the game was stellar, the attendance was not: only 1000 fans saw it. The following week Stearns Advertising Co. sued the team for $1,000, and the court placed it in receivership. The players were stranded on the road in Philadelphia. The team was disfranchised by the league and disbanded.