Prior to the start of the 2010 MLS season, the Crew began play in the CONCACAF Champions League, with a quarterfinal-fixture against Group C-winner, Toluca of Mexico.

During Group Stage, the Crew finished in a second place in their group with an even 2-2-2 record, narrowly edging the Costa Rican champions Saprissa to become the only American club in the knockout stage. On February 22, 2010; Columbus hosted Toluca before 4,500 people at Crew Stadium for the first leg. For the match, Columbus would be missing veteran striker Guillermo Barros Schelotto and defender Frankie Hejduk.

In the match, Mexican-international Sinha opened the scoring giving Los Rojos a critical away goal and the lead over the Crew. Following the goal near misses from Steven Lenhart and Eddie Gaven later on in the half almost drew things level. Shortly before halftime, however, Antonio Ríos doubled the lead for Toluca giving them a very strong advantage. However, the Rojos would reliniquish their lead in the second half. Lenhart would bag a pair of goals in the 66th and 83rd minute of play to draw the match back on parity, and the Crew would head to Toluca tied at two on aggregate.

Columbus began their fifteenth Major League Soccer regular season at home with a 2-0 win in a match against Toronto FC on March 27, 2010.

As of Aug 5, 2010.

Note: Flags indicate national team as defined under FIFA eligibility rules. Players may hold more than one non-FIFA nationality.

Starting XI vs. Colorado on Oct. 23:

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