The 23-year-old outfielder was the Most Valuable Player in last year’s Arizona Fall League, where major league clubs send their top prospects each autumn.
But Desme, a lifelong Catholic, plans to enter a seminary this summer.
“I was doing well at baseball. But I really had to get down to the bottom of things – I love the game, but I aspire to higher things,” he explained.
“I wasn’t at peace where I was at. I have no regrets.”
Desme, who had looked set to receive an invitation to spring training with Oakland’s major league players next month, had been considering the move for over a year, despite hitting 31 home runs and stealing 40 bases in the minor leagues in 2009.
“Last year before the season started, I really had a strong feeling of a calling and a real strong desire to follow it. I just fought it,” he explained.
“As the year went on, God blessed me. I had a better year than I could have imagined, but that reconfirmed my desire.
“I felt that while baseball is a good thing, I thought it was selfish of me to be doing that when I really felt that God was calling me more.”
He informed the A’s management on Thursday evening, and now expects to begin “a 10-year process” towards becoming a priest while he studies at St Michael’s Abbey in Orange County.
Oakland general manager Billy Beane added: “We respect Grant’s decision and wish him nothing but the best in his future endeavours.”