The 2021–22 NAFU Regions League was the third edition of the NAFU Regions League a quaternary association club football tournament for CONCACAF teams located in the North American Football Union countries.
The tournament was heavily altered due to the ongoing COVID-19 pandemic, and retained much of the same format of the 2020–21 edition. Qualification was anticipated to begin in late June 2021 but was postponed to September 2021.
The format for the NAFU Regions League changed this season, with five Mexican, five American, and four Canadian clubs earning a berth into the group stage. Group stage was expanded into 16 teams with four groups of four. The remaining two group stage spots were determined via a qualification tournament amongst teams from Acadiana, Cascadia, Greenland, Iroquois, Navajo, Nunavut, Quebec, and Saint Pierre and Miquelon.
The revised schedule of the competition is as follows (all draws are held at the NAFU headquarters in New York City, United States, unless stated otherwise).