The 1921 Giro di Lombardia was the 17th edition of the Giro di Lombardia cycle race and was held on 10 November 1921, on a course of . The race started and finished in Milan. The race was won by the Italian Costante Girardengo, who reached the finish line at an average speed of , preceding his compatriots Gaetano Belloni and Federico Gay.
67 cyclists departed from Milan and 32 completed the race.
General classification Final general classification Rank Rider Team Time 1 Stucchi-Pirelli 2 Bianchi-Dunlop + 0" 3 Bianchi-Dunlop + 0" 4 Legnano-Pirelli + 0" 5 Bianchi-Dunlop + 0" 6 Individual + 0" 7 Individual + 0" 8 Individual + 0" 9 Legnano-Pirelli + 0" 10 Legnano-Pirelli + 0"
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