The 2015–16 CONCACAF Champions League knockout stage was played from February 23 to April 27, 2016.
In the knockout stage, the eight teams played a single-elimination tournament.
Each tie was played on a home-and-away two-legged basis, with the higher-seeded team hosting the second leg.
The away goals rule would be used if the aggregate score was level after normal time of the second leg, but not after extra time, and so a tie would be decided by penalty shoot-out if the aggregate score was level after extra time of the second leg (Regulations, II.
[1] Starting from this season, the higher-seeded team in each tie would host the second leg throughout the knockout stage.