The second round of AFC matches for 2018 FIFA World Cup qualification (and 2019 AFC Asian Cup qualification) was played from 24 May 2015 to 29 March 2016.
A total of 40 teams (teams ranked 1–34 in the AFC entrant list and six first round winners) were divided into eight groups of five teams to play home-and-away round-robin matches. The eight group winners and the four best group runners-up advanced to the third round of FIFA World Cup qualification as well as qualify for the 2019 AFC Asian Cup finals.
A total of 24 teams eliminated from World Cup qualification in the second round competed in the third round of 2019 AFC Asian Cup qualification (which was separated from the third round of 2018 FIFA World Cup qualification), where they were divided into six groups of four teams and competed for the remaining slots of the 2019 AFC Asian Cup. The 24 teams consisted of the 16 highest ranked teams eliminated in the second round, and the eight teams that advance from the play-off round of 2019 AFC Asian Cup qualification which are contested by the remaining 12 teams eliminated in the second round.
The draw for the second round was held on 14 April 2015, at 17:00 MST (UTC+8), at the JW Marriott Hotel in Kuala Lumpur, Malaysia.
The seeding was based on the FIFA World Rankings of April 2015 (shown in parentheses below). The 40 teams were seeded into five pots:
Each group contained one team from each of the five pots. The fixtures of each group were automatically decided based on the respective pot of each team.