Famous guests of the hotel have included Rudolph Valentino, Mary Pickford, Douglas Fairbanks Sr., Joan Crawford, Spencer Tracy, Katherine Hepburn, Betty Grable, Tyrone Power, Bette Davis, Zsa Zsa Gabor, Vincent Price, Tennessee Williams, and Truman Capote.

Named after Timothy Blackstone, the president of the Illinois Central Railroad who built the hotel mainly to serve passengers of his trains.

A twin tower was originally planned on Wabash Avenue, behind this building and perpendicular in orientation.

In 1920, the Republican Party met in the Blackstone Hotel and chose Warren Harding as its candidate for President. These meetings were the inspiration for the phrase "smoke-filled rooms", coined by a reporter covering the nomination process.

The mansard roof was originally decorated with small spires around the perimeter, and 2 very tall flagpoles or spires.

The poet Carl Sandburg celebrated his 75th birthday in this hotel.

At least 12 U.S. Presidents have stayed here: Theodore Roosevelt, Taft, Wilson, Harding, Coolidge, Hoover, Franklin Roosevelt, Truman, Eisenhower, Kennedy, Nixon, and Carter.

Opera tenor Enrico Caruso was present at the opening of the hotel.

Chicago mayor Richard J. Daley used this hotel for several receptions, including his sons' weddings.

A conversion to luxury condominiums in a restoration by Lucien Lagrange & Associates architects was announced in 2001, but never got off the ground.

The hotel was sold again in December 2004 and will be restored as a Marriott Renaissance Hotel.