Merchant and marine architect Asa Tift built the substantial limestone house on Whitehead Street around 1851, using locally quarried stone and a design suited to Key West's heat. Verandas, tall openings, high ceilings, and a raised principal floor promoted air circulation and protected living spaces. The property survived the Civil War, storms, and shifts in Key West's maritime economy before Pauline Pfeiffer's wealthy uncle purchased it for Pauline and her husband, Ernest Hemingway, in 1931. They restored the neglected residence and made it their family home.

Hemingway had already achieved fame through works including The Sun Also Rises and A Farewell to Arms. In Key West he fished, socialized, traveled to Cuba and Spain, and developed relationships that fed his public image. A second-story studio above a carriage house gave him dedicated writing space. During the 1930s he worked on or completed Death in the Afternoon, Green Hills of Africa, To Have and Have Not, and stories set partly among Depression-era Key West residents. Pauline managed the household while raising their sons Patrick and Gregory.

The couple installed the island's first large in-ground residential swimming pool in the late 1930s at great expense. Hemingway's relationship with journalist Martha Gellhorn contributed to divorce from Pauline in 1940, after which he moved his principal residence to Cuba. Pauline retained the Key West property until her death in 1951. Hemingway died in Idaho in 1961. Later owners preserved furnishings and associations and opened the house as a museum in the 1960s, transforming a private residence into a curated literary destination shaped by family recollection and tourism.

The house, studio, gardens, pool, boundary walls, and numerous furnishings survive, though repairs, hurricanes, climate, visitor traffic, and museum operation have required continuing renewal. Famous polydactyl cats live on the grounds and are presented as descendants of Hemingway-era cats, but stories about the first six-toed cat vary and should not replace documented history. Rooms are arranged to evoke the 1930s rather than frozen untouched since Hemingway's occupancy. Modern safety systems, visitor paths, retail functions, and animal care coexist with authentic nineteenth-century fabric and period objects.

The privately operated Ernest Hemingway Home and Museum owns and manages the National Historic Landmark. Admission is ticketed, with guided interpretation and independent time in the gardens under current visitor rules. The site is not the only important Hemingway residence, nor did every famous work originate in the studio. Its value lies in the relationship between a durable Key West house, a particular decade of the author's career, Pauline Pfeiffer's role, local social and maritime life, later legend-making, and the practical conservation of a heavily visited home in a hurricane-prone climate.