The 2020–21 NAFU Regions League qualifying phase and play-off round began on 10 September and ended on 1 October 2020.
A total of 16 teams competed in the qualifying system of the 2020–21 NAFU Regions League, which includes the preliminary round and the play-off round. The four winners in the play-off round advance to the group stage, to join the four teams that enter in the group stage.
Due to the ongoing COVID-19 pandemic, all qualification matches were held on a neutral site to create a "bubble" to minimize contamination of SARS-CoV-2. All preliminary and first round qualification matches, for the 2020–21 edition only, were moved to Cobb Stadium near Miami, Florida, United States. The play-off round matches served as a test case to admit spectators to CONCACAF competitions with stadia at 20 per cent capacity. The play-off matches were held at Inter Miami CF Stadium and Hard Rock Stadium in the Miami metropolitan area.