He replaces Lee Newman, who leaves the agency this week to join Ogilvy & Mather Chicago as president.
Mills, who has taken up the role with immediate effect, will partner with executive creative directors Mark Bernath and Eric Quennoy to lead the office.
Mills joined W+K Amsterdam in February 2010 as group account director on Heineken and head of business development.
He has overseen the development of the independent agency's relationship with the brewer, expanding it to Brazil, India and the US.
Prior to W+K Amsterdam, Mills held roles at JWT New York and BBH in London and New York.
Bernath and Quennoy said: "Spending the last two years making the Heineken work with Clay has been one of the more enjoyable experiences of our careers. You have to work with people who make work feel more like having fun. That's when the best stuff happens."
In October last year, W+K Amsterdam launched its first independent digital product agency, called The Dam Armada.
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