The Mayflower Hotel (now the Hilton Checkers Hotel) is built on a lot only sixty feet wide and 160 feet deep. The architect, Charles Whittlesey, was known for his hotel designs, which include the El Tovar (1905) at the Grand Canyon and the Wentworth Hotel (1906) in Pasadena (now the Ritz-Carlton, Huntington Hotel & Spa). The Mayflower's façade features ornate Spanish-style ornament. Swirls, checkerboard patterns, and stylized gargoyles abound on the façade's lower three floors. Originally, bas-relief sculptures of the famous ships Mayflower and Santa Maria graced either side of the entry.

While the hotel's exterior is Spanish in style, the original interior leaned more toward "Pilgrim Revival." The ground-floor lobby included the Mayflower Tavern and Ye Bull Pen, a popular eatery decorated in a cattle shed motif. The hotel underwent a major renovation in the 1980s, when two floors were added on top of the building (to house the physical plant as well as a health spa for guests). The guest rooms, originally numbering 348, were enlarged and their number reduced to 188.