He started in his first MLB game for the Toronto Blue Jays on August 7, 2010 against the Tampa Bay Rays. In his first MLB at-bat, Arencibia hit a two-run home run on the first pitch from James Shields, becoming the 28th player in history to hit a home run on his first MLB pitch. In his following plate appearances, he hit a double, a single and then a solo home run and received a curtain call from the fans at the Rogers Centre while finishing the game just a triple shy of hitting for the cycle. Arencibia is the fifth player ever to hit two home runs in his first game. In addition, he became the first person in the modern era with four hits and two home runs in an MLB debut, a feat set 121 years before by Columbus Solons catcher Charlie Reilly.