[9] The foundation's stated purpose is to support "creative people, effective institutions, and influential networks building a more just, verdant, and peaceful world".

[6][10] MacArthur's grant-making priorities include mitigating climate change, reducing jail populations, decreasing nuclear threats, supporting nonprofit journalism, and funding local needs in its hometown of Chicago.

[19] John D. MacArthur owned Bankers Life and Casualty and other businesses, as well as considerable property holdings in Florida and New York.

Their attorney, William T. Kirby, and Paul Doolen, their chief financial officer, suggested that the family create a foundation to be endowed by their vast fortune.

"[23] Between 1979 and 1981, John's son, an ideological opponent of his father with whom the elder MacArthur had an acrimonious relationship, waged a legal battle against the foundation for control of the board of directors.

[25][26] John E. Corbally, the first president of the foundation and later board chairman from 1995 to 2002, was followed in 1989–99 by Adele Simmons, who was the first female dean at Princeton University.

[27][29] Robert Gallucci, formerly dean of Georgetown University's School of Foreign Service, served as the foundation's fourth president from 2009 to 2014.

Nominators, serving confidentially, anonymously and for a limited time, are invited to recommend potential Fellows.

[38] In June 2016, the foundation requested "proposals promising real progress toward solving a critical problem of our time in any field or any location".

In December 2017, the foundation announced that the winning proposal was submitted by the Sesame Workshop and the International Rescue Committee.