McCain, 68, who will replace David Beasley in April, tweeted that she was "deeply honored" to take over at the helm of an organization which has been getting emergency aid to people for nearly six decades.
Beasley tweeted that McCain was taking over in a period when "conflicts, climate shocks & hunger soar."
The heiress to the Hensley Beverage Company in Phoenix, McCain is the widow of John McCain, the unsuccessful 2008 presidential candidate and Republican U.S. senator from Arizona figure who died in 2018.
She is currently the United States' permanent representative to the U.N. agencies in the Italian capital.
WFP, which won the Nobel Peace Prize in 2020, provided aid to 158 million people in 2022, and received $14 billion in funding.
The United States is the agency's largest contributor, ahead of Germany, Canada and Sweden.