The Pope will be on the side of a building on the corner of 34th Street and 8th Avenue in New York's Manhattan.
Francis is due to visit Washington, New York and Philadelphia from September 22.
He will celebrate Mass in Madison Square Garden, close to the work of art, which has been drawing attention from locals and tourists.
The image is being put up by DeSales Media Group on behalf of the Roman Catholic Diocese of Brooklyn.
"This is our way to say 'welcome' and evangelize in the heart of this culturally-diverse city. I am convinced that Pope Francis' apostolic visit will impact everyone, touching hearts across different backgrounds and beliefs," said Monsignor Kieran Harrington, Chairman of DeSales Media Group.
The 225-foot tall billboard will also feature the words Welcome Pope Francis and the public hashtags #PopeInUSA and #PapaEnUSA.
