"[8] Famous visitors included presidential hopefuls James Garfield, Grover Cleveland, Ulysses S. Grant, William Jennings Bryan, and William McKinley; writers Mark Twain, L. Frank Baum, and Oscar Wilde; actresses Sarah Bernhardt and Eleonora Duse, and French cabaret singer Yvette Guilbert in 1897.

By the 1920s, the business in downtown Chicago could support a much larger facility, and the Palmer Estate decided to erect a new 25-story hotel.

It hired Holabird & Roche to design the building, and their team included architect Richard Neutra in a junior role.

[11] The architecture firms of Loebl Schlossman & Hackl and David Fleener Architects completely renovated and restored the hotel between 2007 and 2009.

In 1970, the hotel was the site of the murder of Evelyn Okubo, a young Japanese-American racial justice activist attending a Japanese American Citizens League convention held there.

[15] Entertainers who have appeared at the Palmer House's Empire Room have included Frank Sinatra, Judy Garland, Liberace, Ella Fitzgerald, Maurice Chevalier, Lena Horne, Nat King Cole, Louis Armstrong, Harry Belafonte, Sammy Davis Jr., Peggy Lee, Carol Channing, Bobby Darin, Jimmy Durante, Sonny & Cher, Liza Minnelli, Dionne Warwick, Sophie Tucker, Tommy Dorsey, Phyllis Diller, Lou Rawls, Shep Fields (1930s) [16][17] Dick Gregory (1963), Frankie Laine (1963), Josh White (1966), Tony Bennett (1968), Florence Henderson (1968), Donald O'Connor (1971), Jerry Lewis (1971), The Supremes (1971 & 1972),Jane Powell (1972), Lorna Luft (1972), Trini Lopez (1973), The Lettermen (1973) and many others.