The qualified teams were seeded in the knockout stages according to their results in the second stage, with the group winners seeded 1–8, and the group runners-up seeded 9–16.
Each tie was played on a home-and-away two-legged basis, with the higher-seeded team hosting the second leg. However, CONMEBOL required that the second leg of the finals must be played in South America, i.e., a finalist from Mexico must host the first leg regardless of seeding.
In the finals, if tied on aggregate, the away goals rule was not used, and 30 minutes of extra time was played. If still tied after extra time, the penalty shoot-out was used to determine the winner.
If there were two semifinalists from the same association, they must play each other.
Bracket
The bracket of the knockout stages was determined by the seeding as follows:
The first legs were played on April 24–25 and April 30–May 2, and the second legs were played on May 8–9 and 14–16, 2013.
Match A
---- Atlético Mineiro won 6–2 on aggregate.
Match B
---- Tied 2–2 on aggregate, Santa Fe won on away goals.
Match C
---- Olimpia won 3–2 on aggregate.
Match D
---- Boca Juniors won 2–1 on aggregate.
Match E
---- Tied 2–2 on aggregate, Newell's Old Boys won on away goals.
Match F
---- Fluminense won 3–2 on aggregate.
Match G
---- Tied 1–1 on aggregate, Real Garcilaso won on penalties.
Match H
---- Tijuana won 2–1 on aggregate.
Quarterfinals
The first legs were played on May 22–23, and the second legs were played on May 28–30, 2013.
Match S1
---- Tied 3–3 on aggregate, Atlético Mineiro won on away goals.
Match S2
---- Santa Fe won 5–1 on aggregate.
Match S3
---- Olimpia won 2–1 on aggregate.
Match S4
---- Tied 0–0 on aggregate, Newell's Old Boys won on penalties.
Semifinals
The first legs were played on July 2–3, and the second legs were played on July 9–10, 2013.
Match F1
---- Tied 2–2 on aggregate, Atlético Mineiro won on penalties.
Match F2
---- Olimpia won 2–1 on aggregate.
Finals
The finals were played on a home-and-away two-legged basis, with the higher-seeded team hosting the second leg. The teams tied on aggregate, the away goals rule was not used, and 30 minutes of extra time were played. A penalty shoot-out was used to determine the winner. The first leg was played on July 17, and the second leg was played on July 24, 2013. ---- Tied 2–2 on aggregate, Atlético Mineiro won on penalties.