Frankie Dettori is to leave Godolphin after 18 years with the stable.
The 41-year-old could still ride in the blue colours on a freelance basis, with Mickael Barzalona and Silvestre de Sousa their retained riders for 2013.
"Godolphin has been a major part of everything I have achieved in racing," said Dettori, who rode nine English Classic winners with the team.
"I feel the time has come for a change. My position in the stable has changed a little bit and I need a new challenge."
Dettori rode Godolphin's first Classic winner, Balanchine, in 1994 and had 110 Group or Grade One victories for Sheikh Mohammed's operation.
"Sheikh Mohammed has been an unbelievable boss to me," Dettori said. "He had the confidence to take me on board when I was young and we smashed every record together.
"I will be forever grateful to him for everything he has done for me and for my family."
Frenchman Barzalona, 21, who won the 2011 Derby as a 19-year-old on his debut in the race, joined Godolphin in March and has shared top billing in the team with the legendary Italian.
Godolphin's racing manager, Simon Crisford, said: "We have had a tremendous association with Frankie over many years.
"He has achieved so much on behalf of Godolphin and has made the difference between winning and losing on so many occasions in the world's biggest races.
"Frankie is looking for a fresh challenge and we felt that the retainer was not really working so this is the best way forward.
"We have had many great days together and we look forward to working with Frankie in the future and hopefully enjoying more success together."
Speaking to the BBC Sport website on Thursday, Dettori said he planned to continue riding for several years.
"My target is 50, then we'll see," he said. "It is a dangerous sport and when you fall, you get hurt, but touch wood I have been quite lucky and let's hope it carries on that way. There's plenty of good racing in me."
Dettori, who had his first booking in seven years for Godolphin's rivals Ballydoyle when he rode Camelot in the Prix de l'Arc de Triomphe earlier this month, said he was unsure if he would team up with the Irish stable again.
"It was a great honour to be offered the ride and I didn't have anything in the race. Unfortunately the horse didn't win. Who knows what the future holds?" he said.