[4][5] Ryan Williams and David Estrada announced their retirements from professional football,[4][5] and Joris Ahlinvi was released at the end of his contract.

[6] December saw Ilija Ilić, Harry Swartz, and Sergio Rivas join from Indy Eleven, Hartford Athletic, and Reno 1868 FC, respectively.

[7][8][9] In January 2021, the club announced the signings of Isidro Martinez from Rio Grande Valley FC Toros and semiprofessional defender Alex Touche.

In March, first-choice goalkeeper Cody Mizell announced he would be departing New Mexico United for a club in Major League Soccer, later revealed to be New York City FC.

[13] New Mexico United began its competitive season away at Rio Grande Valley FC Toros on May 1, beginning the campaign with a 1–0 loss.

They ended the month with a 1–0 loss at home to Atlantic Division opponents Loudoun United FC, in which Austin Yearwood was sent off with a straight red card in the 23rd minute.

[15][16] After beating San Antonio FC at home on June 16, the club ended the month with two away losses to Four Corners Cup teams in 5 days.

On July 28, the club announced the re-signing of Afghan international David Najem, who had left New Mexico United after making 13 appearances in the 2020 season.

[19] Also on August 17, the Albuquerque City Council approved a ballot measure to finance construction of a soccer-specific stadium by gross tax receipt bonds.

The club lost the first of its 7 matches in October away at Louisville City FC, losing 3–1 as their captain Paolo DelPiccolo scored twice in the opening 15 minutes.

Despite winning their final game of the season 3–1 at home to Real Monarchs, other results left the club 5th in the Mountain Division, and out of the USL Championship playoffs.

[32] On January 21, the USL Board of Governors announced the format for the 2021 season, which would divide the Eastern and Western Conferences into two smaller divisions.