De Nardis, who will be based in New York, will take up the role in the first quarter of 2009.
He will report to Daryl Simm, chairman and chief executive of Omnicom Media Group.
De Nardis replaces Joe Uva who left OMD Worldwide in early 2007. Uva left to take up a position at Spanish-language media giant Univision Communications.
Simm said: "Mainardo is a true global media leader who brings a rare combination of international media expertise, client service understanding and operating skill.
"OMD's recent global business success underscores how well Mainardo's international credentials fit the emerging needs of our clients; he has the right skill set to build on OMD's position as the world's leading media service company."
De Nardis has more than 20 years experience in the business. He was most recently based in London as global chief executive of Aegis Media; however in May of this year he suddenly resigned from this role after two years in the position.
Earlier in his career, de Nardis was joint chief executive, alongside Charles Courtier, at media agency CIA when it merged with The Media Edge to become Mediaedge:cia.
He and Courtier were subsequently named joint global chief executives of the combined companies and established them as a single global media network.
De Nardis said: "I've long admired the Omnicom culture as well as OMD's reputation as the most awarded media network and its roster of category-leading clients.
"I'm very excited about leading this tremendous team at a time when media communication is playing an ever more critical role in the success of client business plans."
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