The strategic collaboration will focus on harnessing better results from three key components of digital marketing - content, performance and audience.
The two companies will explore technologies and methodologies aimed at enhancing engagement, performance and return on investment.
As part of the agreement, Starcom MediaVest Group, ZenithOptimedia and Digitas will be among the first agency networks to use Microsoft Advertising's new planning and buying technology, Admira, set to launch in the fourth quarter.
Microsoft will also continue its ongoing commitment to Publicis Groupe's research initiative The Pool, which tests new video ad formats through its VivaKi Nerve Centre.
It follows Publicis Groupe chairman Maurice Levy launching VivaKi last year on the principle of "open source pursuit of digital solutions for clients".
Another initiative will see Microsoft support a new content studio that will help the Publicis-owned studio PBJS create large scale, global programming opportunities.
David Kenny, managing partner of VivaKi and a member of the Publicis Groupe Directorie, said the partnership represented "the smartest approach to keep marketers ahead of the curve".
The collaboration follows Microsoft announcing a new strategic alliance with Sir Martin Sorrell's WPP Group earlier this week, aimed at exploring the dynamics between search engine marketing and brand building.
Darren Huston, corporate vice-president of Microsoft Corp's Consumer and Online group, said the latest agreement reflects the company's commitment "to partner with the world's largest agencies to drive new ideas and innovations that address the complex marketing needs and challenges facing advertisers today".