McDonald also manages other artistes such as Passion Pit, St Lucia, and Ray LaMontagne, said the Hollywood Reporter.
"After 13 years, John and I are parting ways. It's been a magnificent journey, which began before his debut album, and along the way has included seven Grammy awards, years of massively successful tours around the world, and over 20 million albums sold," McDonald said.
"I hold John's talent in the highest regard and wish him nothing but the best," he added.
Mayer is currently in the second leg of his concert tour in North America.