Since its inception, The New Yorker Hotel has welcomed many famous people over the years. In addition to celebrities from the early years of its history, The New Yorker Hotel hosted President John F. Kennedy (when he was a Senator and running for the presidency), boxer Muhammad Ali (after his legendary duel with Joe Frazier in the "Fight of the Century" in 1971), and Cuban leader Fidel Castro (who stayed here the last time he visited Manhattan).

Academy Award winning actress Jennifer Hudson from Dreamgirls stayed at The New Yorker Hotel in December 2006 and presidential hopeful Senator Hillary Clinton used The New Yorker Hotel's ballroom as her campaign headquarters on Super Tuesday, February 5, 2008.