He attended Shawnee High School, in Medford, New Jersey, where he was a stand-out pitcher and broke the state record for most strikeouts in a game. Sean was also a great hitter and led Shawnee to a state championship. Doolittle played for the University of Virginia Cavaliers baseball team as both a starting pitcher and first baseman. He formerly held the record for wins in a career for a Virginia pitcher — 22 — which has since been passed by Danny Hultzen. In 2005 and 2006, Doolittle was named to the USA National (Collegiate) Baseball Team.
Despite being injured for most of the 2009 season, Doolittle was ranked tenth in Oakland's farm system according to Baseball America. Doolittle missed the entire 2010 season while rehabbing from 2 knee surgeries. In the 2011 offseason, he was place on Oakland's 40-man roster to be protected from the rule 5 draft. After missing more than 2 years, Doolittle converted back to pitching, making his professional pitching debut in the instructional league in Arizona in 2011.