[1] Coquimbo Unido were the champions, winning their fourth title in the competition as well as clinching promotion to Primera División with a 2–1 victory over Fernandez Vial on 13 November, the last matchday of the regular season.
[2] The tournament was played by 16 teams, 12 returning from the previous season, three relegated from Campeonato Nacional (Coquimbo Unido, Deportes Iquique and Universidad de Concepción), and the Segunda División Profesional champions.
The 16 teams play each other in a double round-robin tournament (once at home and once away) for a total of 30 matches.
[3] Originally, Lautaro de Buin were to take part in the competition as 2020 Segunda División Profesional champions,[4] but the club was suspended per ruling by ANFP's Court of Justice due to irregularities with the contracts of their players, and later expelled from the ANFP on 5 May 2021.
[5][6] Following an appeal by Lautaro de Buin, on 10 June 2021 the original ruling was changed to a six-point deduction in the Segunda División standings, thereby losing the first place and declaring Fernandez Vial as Segunda División champions, who in turn also took Lautaro's place in Primera B.