The knock-out stage of the 2013 AFC Cup was played from 14 May to 2 November 2013. A total of 16 teams competed in the knock-out stage.

The winners and runners-up of each of the eight groups in the group stage qualified for the knock-out stage. Both West Asia Zone and East Asia Zone had eight teams qualified.

In the knock-out stage, the 16 teams played a single-elimination tournament. In the quarter-finals and semi-finals, each tie was played on a home-and-away two-legged basis, while in the round of 16 and final, each tie was played as a single match. The away goals rule (for two-legged ties), extra time (away goals do not apply in extra time) and penalty shoot-out were used to decide the winner if necessary.

The schedule of each round was as follows.

In the round of 16, the winners of one group played the runners-up of another group in the same zone, with the group winners hosting the match. The matchups were determined as follows:

The draw for the quarter-finals, semi-finals, and final (to decide the host team) was held on 20 June 2013, 15:00 UTC+8, at the AFC House in Kuala Lumpur, Malaysia. In this draw, teams from different zones could play each other, and the "country protection" rule was applied: if there are two teams from the same association, they may not play each other in the quarter-finals.

The matches were played on 14 and 15 May 2013.

The first legs were played on 17 September 2013, and the second legs were played on 24 September 2013.