After starting the 2009 season in the minors, Cervelli was called up by the Yankees on May 5, 2009, when Jorge Posada was placed on the 15-day disabled list, though he was batting only .190, with a .266 on-base percentage and .310 slugging percentage at Trenton at the time of the call-up, and had not played in Class AAA. He made his first major league start on May 7, after José Molina injured his quad. He recorded his first major league hit, a single, on May 8, against the Baltimore Orioles, while also catching starting pitcher CC Sabathia during a complete game shutout. Cervelli asserted himself as a reliable defensive catcher for the New York Yankees, and received praise from his teammates. Though Cervelli was sent to the Scranton/Wilkes-Barre Yankees of the Class AAA International League on July 8, 2009. when Molina was activated off of the disabled list, Yankees' manager Joe Girardi made clear that he was impressed with Cervelli's performance.
On June 24, 2009, Cervelli hit his first major league home run against Kris Medlen of the Atlanta Braves, breaking up a no-hitter. On September 16, Cervelli had his first walk-off hit – a single in the bottom of the ninth inning against the Toronto Blue Jays. Cervelli was a member of the Yankees roster in the 2009 MLB postseason, as the Yankees won the 2009 World Series, but he was not on the World Series roster.
Cervelli played for the Italy national baseball team in the 2009 World Baseball Classic and the 2017 World Baseball Classic.