Joining the Florida land boom party late, Hotel Knox opened in 1928. It touted its large rooms with hot water and comfortable steam heat throughout the building. Room rates were $1.50 and up per night or $7.00 and up per week. Even though business got tough in the early 1930s as the Great Depression hit, the hotel persevered.

In 1944, H.K Watson, owner of the hotel, died. By then, he owned several Knox stores and only wintered in Tampa. In 1945, his heirs sold the hotel for $90,000 to Knox Stores, Watson's former corporation. The Jeflafay Corporation bought the property in 1959 for $250,000. They kept the hotel and its restaurants, barbershops, and cleaners going until 1961 when The Hillsborough County Commission purchased the property for $328,000 as a site for erecting a new county courthouse annex. The projected cost for the new building was $1.75 million. The hotel sat tattered and empty for two years while the county wrote plans and dealt with infighting. It was finally demolished in March of 1963, and the new annex opened in February 1965 at a final cost of $2.2 million.

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