The knockout phase involved 32 teams: 24 teams which qualified directly, and the eight group winners from the qualifying round. Each tie in the knockout phase, apart from the final, was played over two legs, with each team playing one leg at home. The team that scored more goals on aggregate over the two legs advanced to the next round. If the aggregate score was level, the away goals rule was applied, i.e. the team that scored more goals away from home over the two legs advanced. If away goals were also equal, then 30 minutes of extra time was played. The away goals rule was again applied after extra time, i.e. if there were goals scored during extra time and the aggregate score was still level, the visiting team advanced by virtue of more away goals scored. If no goals were scored during extra time, the tie was decided by penalty shoot-out. In the final, which was played as a single match, if scores were level at the end of normal time, extra time was played, followed by penalty shoot-out if scores remained tied. The mechanism of the draws for each round was as follows:
In the draw for the round of 32, the sixteen teams with the highest UEFA coefficients were seeded, and the other sixteen teams were unseeded. The seeded teams were drawn against the unseeded teams, with the seeded teams hosting the second leg. Teams from the same association could not be drawn against each other.
In the draw for the round of 16, the eight teams with the highest UEFA coefficients were seeded, and the other eight teams were unseeded. The seeded teams were drawn against the unseeded teams, with the seeded teams hosting the second leg. Teams from the same association could not be drawn against each other.
In the draws for the quarter-finals onwards, there were no seedings, and teams from the same association could be drawn against each other.
Qualified teams
Below are the 32 teams which participated in the knockout phase.
Bracket
Round of 32
The draw for the round of 32 was held on 20 August 2015.
Seeded
Unseeded
;Notes The first legs were played on 7 and 8 October, and the second legs were played on 14 and 15 October 2015.
Round of 16
The draw for the round of 16 was held on 19 October 2015.
Seeded
Unseeded
The first legs were played on 11 and 12 November, and the second legs were played on 18 and 19 November 2015.
Quarter-finals
The draws for the quarter-finals and semi-finals were held on 27 November 2015. The first legs were played on 23 March, and the second legs were played on 30 March 2016.
Semi-finals
The first legs were played on 24 April, and the second legs were played on 1 and 2 May 2016.
