The tournament began on 19 March 2022 and ended on 13 November 2022, with the final match on neutral ground.
[1][2][3] Magallanes won their first Copa Chile title, defeating Unión Española 7–6 on penalty kicks after a 2–2 draw in the final.
Ties in this round were single-legged, with the team from the lower tier hosting the match.
The 14 first stage winners, as well as San Bernardo Unido who advanced as best loser, were drawn against 15 Primera B de Chile teams according to geographical and safety criteria, with the remaining two Primera B teams being drawn against each other.
Like the previous stage of the competition, ties in this round were single-legged, with the team from the lower tier hosting the match.