VML won the £2 million brief following a competitive pitch process managed direct by Virgin Active, which included AKQA.
The fitness chain had previously appointed Karmarama as its lead creative agency in 2013 with a multimillion-pound brief to make it "the most-loved health club in the UK."
VML's brief is to bring about what it hopes will be a "paradigm shift along the entire customer journey" as it aims to engage its customers with its brand.
Chris Wood, managing director at VML, said: "We are delighted, possibly on the border of being over-excited, about working with Virgin Active.
"We believe wholeheartedly in the customer proposition of 'living happily ever active', and love working with a brand and team at Virgin Active that is brimming with personality and energy."