In a statement, Global said that it had agreed with Vaughan that it was the "right time" for him to step down. This morning's broadcast was his last.
Vaughan's co-host Lisa Snowdon will continue on Capital FM's London breakfast show, joined on Monday (November 21) by drivetime DJ Greg Burns. A permanent replacement for Vaughan will be announced "in due course".
"I have just loved doing this job but after all these years of getting up in the middle of the night, I really think the time is right to hand over the microphone to someone else," said Vaughan, who took over the show in 2004 from Chris Tarrant.
"It's been a joy waking up London every morning and a thrill to have been part of the broadcasting tapestry of this great city."
Vaughan and Snowdon's show was the most popular commercial breakfast radio programme in London, according to the latest RAJAR data, attracting 1.14m listeners each week.
The duo were ahead of Neil Fox on Magic FM with 854,000 weekly listeners, and Jamie Theakston and Harriet Scott on Heart with 792,000.
Global Radio director of broadcasting Richard Park said: "Johnny has done a fantastic job over the years, particularly recently, building the programme with Lisa Snowdon, into London's most popular commercial radio breakfast show.
"Johnny is a skilled broadcaster on radio and television, and we thank him for his time with 95.8 Capital FM, while wishing him every success for the future."
Snowdon, who replaced Denise Van Outen as Vaughan's breakfast co-host in 2008, said in September that she was yet to make a decision on her future at Capital.
Her contract was due to finish at the end of this year, but a message posted on the Johnnyandlisa Twitter account today said that she is "absolutely staying on".