For most of Serie A's history, there were 16 or 18 clubs competing at the top level. Since 2004–05, however, there have been 20 clubs in total. One season (1947–48) was played with 21 teams for political reasons, following post-war tensions with Yugoslavia. Below is a complete record of how many teams played in each season throughout the league's history;

18 clubs: 1929–1934
16 clubs: 1934–1943
20 clubs: 1946–1947
21 clubs: 1947–1948
20 clubs: 1948–1952
18 clubs: 1952–1967
16 clubs: 1967–1988
18 clubs: 1988–2004
20 clubs: 2004–present

During the season, which runs from August to May, each club plays each of the other teams twice; once at home and once away, totalling 38 games for each team by the end of the season. Thus, in Italian football a true round-robin format is used. In the first half of the season, called the andata, each team plays once against each league opponent, for a total of 19 games. In the second half of the season, called the ritorno, the teams play another 19 games, once more against each opponent, in which home and away matches are reversed. The two halves of the season had exactly the same order of fixtures until the 2021–22 season, when an asymmetrical calendar was introduced, following the format of the English, Spanish, and French leagues. Since the 1994–95 season, teams are awarded three points for a win, one point for a draw, and no points for a loss. Prior to this, teams were awarded two points for a win, one for a draw, and none for a loss. The three lowest-placed teams at the end of the season are relegated to Serie B, and three Serie B teams are promoted to replace them for the next season.

European qualification

As of 2022, Serie A is ranked as the fourth-best league by UEFA coefficient, therefore the top four teams in the Serie A qualify straight to the UEFA Champions League group stage. The team finishing fifth, along with the Coppa Italia winner (if the Coppa Italia winner finishes outside the top five) or the team finishing sixth (if the Coppa Italia winner finishes inside the top five), qualify for the UEFA Europa League group stage. The sixth or the seventh ranked club, depending on the Coppa Italia winner's league performance, joins the final qualification round of the UEFA Europa Conference League.

Tiebreaking

If after all 38 games there are two teams tied on points for first place or for 17th, the last safety spot, the team that wins the scudetto or stay up at 17th is decided by a single-legged play-off game of 90 minutes and penalties (no extra time), to be held at a neutral venue with the designated home team determined by tiebreakers below. If at least three teams are tied for one of those spots, then the two teams to play in the match is decided by a mini table between the teams involved using the tiebreakers below. For a tie in any other position the deciding tie-breakers are as follows:

1.Head-to-head points
2.Goal difference of head-to-head games
3.Goal difference overall
4.Higher number of goals scored
5.Play-off game at a neutral venue if relevant to decide European qualification or relegation; otherwise by coin flip

Between 2006–07 and 2021–22, the tiebreakers currently used for all places to decide the scudetto winner if necessary, though this was never needed. Prior to 2005–06, a play-off would immediately be used if teams were tied for first place, a European qualification spot, or a relegation spot. In some past years, the playoff was a single game at a neutral site while in others it was a two-legged tie decided by aggregate score. A playoff game has never been needed since the tiebreaking format changed.

The only time a playoff was used to decide the champion occurred in the 1963–64 season when Bologna and Inter both finished on 54 points. Bologna won the playoff 2–0 at the Stadio Olimpico in Rome to win the scudetto. Playoff games were used on multiple occasions to decide European competition qualifications (most recently in 1999–2000) and relegation (most recently in 2022–23).