On January 31, 2011, he was sent to Egypt by President Barack Obama to negotiate a resolution to the popular protests against the regime that had swept the country.

[9] In 1976, at the beginning of the Carter administration, he served under Cyrus Vance as Deputy Executive Secretary of the Department of State.

During his tenure in Lusaka, he played the role of point man for the Constructive Engagement policy of assistant secretary of state for African affairs Chester Crocker.

Wisner worked well with Zambian president Kenneth Kaunda and helped to rebuild bilateral relations between Zambia and the USA after a 1980 spy scandal at the U.S. embassy in Lusaka.

Crocker's efforts contributed to the organization and successful discussions at the February 1984 Lusaka Conference regarding conflicts in Angola and Namibia.

In late 2002, Wisner co-chaired an independent working group that developed a model for the US's post-conflict role in Iraq, should an invasion occur.

In 2012 he succeeded Paul A. Volcker as chairman of the board of trustees of International House, a cultural-exchange residence and program center in New York City.