The AFC and its counterpart, the National Football Conference (NFC), each have 16 teams organized into four divisions.

A series of league expansions and division realignments have occurred since the merger, thus making the current total of 16 teams in each conference.

In this way, non-divisional competition will be mostly among common opponents – the exception being the three games assigned based on the team's prior-season divisional standing.

Then-NFL President and owner of the Cleveland Browns Art Modell had suggested of a format in which three teams from the NFL would move to the AFC to create two thirteen-team conferences.

[20][21] The AFL had begun play in 1960 with eight teams before adding two more expansion clubs (the Miami Dolphins in 1966 and the Cincinnati Bengals in 1968) before the merger.

Furthermore, he realized there was an opportunity to establish a lucrative in-state rivalry with the newly-established Bengals, who had been founded by Paul Brown after Modell had forced him out of Cleveland after purchasing the team.

When Modell was visited in the hospital by Art Rooney (owner of the Pittsburgh Steelers) and Wellington Mara (owner of the New York Giants), Modell offered to have his franchise move to the AFC, provided two other "old guard" franchises did so as well and the three affected teams to move were adequately compensated for joining what was still looked down on in NFL circles as a "junior" or "inferior" circuit.

Not wanting to lose his long-established rivalry with Cleveland, the equally cash-strapped Rooney quickly agreed to join the Browns in the AFC.

Upon the completion of the merger of the AFL and NFL in 1970, the newly minted American Football Conference had already agreed upon their divisional setup along mostly geographical lines for the 1970 season; the National Football Conference, however, could not agree upon their setup, and one was chosen from a fishbowl on January 16, 1970.

When the Seattle Seahawks and the Tampa Bay Buccaneers joined the league in 1976, they were temporarily placed in the NFC and AFC respectively.

17 of the 19 AFC champions from 2001 to 2019 have started one of just three quarterbacks - Tom Brady, Peyton Manning and Ben Roethlisberger - in the Super Bowl.