On 15 July 2021, Monza played their first pre-season friendly against Real Vicenza in Ronzone; the match ended in a 14–0 win.

[3] Monza finished their training camp in Ronzone on 24 July, by beating newly-promoted Serie C club Pro Sesto 3–0.

[5] Monza played their last two pre-season friendlies on 4 and 8 August, drawing 1–1 to Pro Patria,[6] and winning 3–0 at home against Giana Erminio.

Key moments included Marco D'Alessandro's stoppage-time goal to help Monza beat Cittadella 1–0,[18] José Machín's 30-meter goal in the 88th-minute which helped his side win 3–2 against Como,[19] Dany Mota's consecutive braces at home against Como and Cosenza,[20] and Monza's first away win of the season, a 2–0 victory over Brescia on 5 December.

[25] In February, after wins against SPAL and Ternana,[26][27] Monza lost their first home game of the season after 11 matches, in a 2–1 defeat against Pisa.

[28] After a 4–1 away win to Pordenone thanks to a Mattia Valoti brace,[29] Monza lost at home once again (1–0 to Lecce), closing February in sixth place.

[33][34] After losing to rivals Como in April,[35] Monza won against Ascoli and Cosenza 2–0, with Valoti and Gytkjær scoring a goal each in both games.

[43] Having finished the regular season in fourth place, Monza gained direct access to the semi-finals of the promotion play-offs.