On November 9, 2021, Detroit City FC announced its departure from NISA to join USL Championship.

2022 USL Championship

March 12, 2022:  at San Antonio FC
March 19, 2022:  Charleston Battery
March 26, 2022:  Pittsburgh Riverhounds
April 2, 2022:  Memphis 901 FC
April 5, 2022:  Michigan Stars (US Open Cup)
April 9, 2022:  at Atlanta United II
April 15, 2022:  Birmingham Legion FC
April 19, 2022:  Columbus Crew SC (US Open Cup)
April 23, 2022: at Hartford Athletic (Match Summary)
April 30, 2022:  New York Red Bulls II
May 7, 2022: at FC Tulsa (Match Summary)
May 10, 2022:  Louisville City FC (US Open Cup)
May 14, 2022:  Loudoun United FC
May 18, 2022:  at Miami FC
May 21, 2022:  Atlanta United II
June 4, 2022: at Pittsburgh Riverhounds (Match Summary)
June 11, 2022:  Sacramento Republic FC
June 18, 2022:  El Paso Locomotive FC
June 25, 2022:  at Memphis 901 FC
July 2, 2022: at Las Vegas Lights FC (Match Summary)
July 6, 2022:  Hartford Athletic
July 9, 2022:  at Indy Eleven
July 16, 2022: at Monterey Bay FC (Match Summary)
July 23, 2022: New Mexico United
August 6, 2022: at Tampa Bay Rowdies (Match Summary)
August 13, 2022: Oakland Roots
August 17, 2022: at Birmingham Legion FC (Match Summary)
August 20, 2022: Louisville City FC
August 29, 2022: at Charleston Battery  (Match Summary)
September 3, 2022: Indy Eleven
September 10, 2022: at Colorado Springs Switchbacks FC (Match Summary)
September 17, 2022: Tampa Bay Rowdies
September 21, 2022: at New York Red Bulls II (Match Summary)
October 1, 2022: at Loudoun United FC
October 5, 2022: at Louisville City FC
October 15, 2022: Miami FC
October 22, 2022: at Memphis 901 FC

Also, the Women’s team moved from UWS to the USL W League

2022 USL W League

May 7, 2022:  Kalamazoo FC
May 12, 2022:  Racing Louisville FC|
May 15, 2022: at Racing Louisville FC (Match Summary)
May 26, 2022:  at Midwest United FC
May 29, 2022:  at Flint City AFC
June 1, 2022:  at AFC Ann Arbor
June 5, 2022:  Kings Hammer FC
June 15, 2022:  AFC Ann Arbor
June 18, 2022:  at Kalamazoo FC
June 28, 2022:  Midwest United FC
July 1, 2022:  Indy Eleven
July 9, 2022: at Indy Eleven