The four-term commissioner announced his decision Wednesday to his staff, to The Associated Press and in a letter to supporters.
Spell was a veterinarian and Richland mayor before he was elected agriculture commissioner in 1995. He took office in January 1996.
Spell was first elected statewide as a Democrat. He switched to the Republican Party in 2005, saying his ideas about government efficiency were a better match with the GOP.
Spell is 67 and says he wants to spend more time with his family.
Agriculture commissioner is one of eight statewide positions up for election in 2011.