Tigre were the champions, winning their first Primera Nacional title by beating Barracas Central by a 1–0 score in the final played on 22 November 2021 and earned promotion to the Argentine Primera División.
Both zone winners played a final match on neutral ground to decide the first promoted team to the Liga Profesional for the 2022 season, while the teams placed from second to fourth place in each zone played a knockout tournament (Torneo Reducido) for the second promotion berth along with the loser of the final between the zone winners, which joined the Reducido in the semi-finals.
No teams were relegated to either Primera B Metropolitana or Torneo Federal A this season.
The semi-finals were contested by the three winners from the previous stage, as well as the Final losers Barracas Central.
The semi-final winners played a match on neutral ground to decide the second team promoted to Primera División.