Matthews is believed to want a break from advertising, and has quit the agency with no new job to go to.
Earlier this year, Matthews' co-head of department Paul Shearer left the agency to become the joint executive creator director of Leo Burnett, with Mother's Jim Thornton.
As well as running the creative department, Matthews had responsibility for the Coca-Cola and Vodafone accounts. He developed the "Eat football, sleep football, drink Coca-Cola" initiative and wrote Vodafone's "How are you?" global campaign.
His most famous work was the Rowan Atkinson Barclaycard campaign he wrote while at BMP DDB.
in the early 90s. The ads, which featured Rowan Atkinson as a hapless secret service agent named Latham, have since been adapted into a feature film entitled Johnny English.
Wieden & Kennedy confirmed that Matthews would be leaving, although no succession plans have yet been announced.
Shearer said: "Jon will be sorely missed. He was the heart and soul and Wieden & Kennedy in Amsterdam."