The Mayo hosted many of Tulsa's most notable 20th-century visitors, including President John F. Kennedy, Bob Hope, Charles Lindbergh, Babe Ruth, Jack Dempsey, Will Rogers,[4] Charlie Chaplin and Mae West.

[5] In William Inge's 1953 Pulitzer Prize winning play, Picnic, the Mayo Hotel is where the lead character Hal intends to find work as a bellhop.

On January 9, 1981, Daon Corp, a Newport Beach subsidiary of a Vancouver-based firm, bought the hotel for $4.6 million, announcing plans to refurbish the property.

[9] Daon closed the hotel in early 1981, for what they announced would be a 12 to 14-month renovation, which would involve restoring the original two-story lobby, combining and enlarging the guest rooms, and adding new dining options.

[10] They proposed various restoration concepts over the 13 years they owned the property, but eventually put it up for sale after Tulsa voters rejected a measure in November 2000 to finance a new convention center, which would have brought more guests to a reopened hotel.

The revenue from the garage financed the renovation of the historic ground floor public rooms, which reopened in 2003 and quickly became a popular venue for galas, proms, receptions and meetings.

[18] Since then, the hotel has hosted numerous famous guests, including OneRepublic, Lady Gaga, James Taylor, Justin Bieber, Bob Seger, Fleetwood Mac, and Josh Groban.

In the 2022 Paramount+ television series Tulsa King, main character Dwight "The General" Manfredi, portrayed by Sylvester Stallone, resides in the Mayo Hotel.