Spence will be responsible for the agency’s growth and its senior client relationships.
M/SIX’s clients include TalkTalk, Ovo Energy and Robinsons. Spence will report to Jess Burley, the global chief executive.
Spence joined Universal McCann in 2011 as the group director overseeing brands including MasterCard and Brown Forman.
Before that, he was a business director at OMD with responsibility for fashion and luxury brands including Estée Lauder.
Spence started his career at Carat in the UK, where he spent five years. He has also worked at Mindshare.
He said: "M/SIX was the standout agency of choice for me, having the talent, ambition and freedom to stand shoulder to shoulder with and even surpass the biggest network agencies out there. I’m looking forward to being part of making that a reality."
Spence is relocating to the UK for family reasons.
Last week, M/SIX, a joint venture between The & Partnership and WPP, lost its Carphone Warehouse account to Walker Media in a review that was prompted by the merger of Dixons Retail and Carphone Warehouse last year.