Colangelo will be replaced by sports agent Jeff Moorad, who said he had resigned from the agency that bears his name.
Colangelo said he would give up his CEO duties after this season and then step down as board chairman after the 2005 campaign.
"As I have stated on several occasions, my professional life has been in a transition stage over the last few months and this reorganization continues that trend," said Colangelo.
"As for Jeff, I've known him for an awfully long time, working with him over the years in a variety of different endeavors. He's a person I have the utmost respect for and know that this transition will be a seamless one for him."
The Diamondbacks set the record for the shortest time between playing the franchise's first game and winning the World Series. They won the championship in 2001 in seven games over the New York Yankees.