The pair, who both write and art direct, created the "life's one long catwalk" series of ads for Clarks, the account they co-ran as creative directors.
At O&M they will work as a senior creative team across a selection of accounts.
During a five-year spell at St Luke's, Chalkley and Simons have been responsible for creating work for BT, Ikea, Sky and the Government. Chalkley's work on Ikea won two Cannes Lions.
He launched his advertising career at Ammirati Puris Lintas in 1993 as an art director, working on Peperami, Batchelors Cup a Soup and Rover - for which he won a gold at the Aerial Awards.
In 1998, he moved to St Luke's as a senior creative, and was promoted to creative director in 2000 as part of an overhaul of the department.
Simons was employed by Bates for two spells before joining St Luke's in 1999. He created the first TV campaign for Superdrug, which won a bronze and silver at the British Television Advertising Awards.
Malcolm Poynton, the executive creative director at O&M, said: "Chalkley and Simons are incredibly fresh thinkers who will be a real asset to the agency."