The first two decades of the new century brought Alachua County's agricultural-based economy troubled times as the boll weevil blighted the cotton crops, while World War I brought an end to the phosphate industry in the area. Still, one of the most significant events in the history of the county occurred in 1905, when Gainesville was chosen as the site for the University of Florida. When the university opened a year later, it had only 102 students, 15 faculty and two unfinished buildings.
Twenty years later, the student body numbered 2,000, and students went to classes in 13 Gothic buildings, including a library, a gymnasium and an auditorium. By the 1930s, the university had become the most important staple in the county's economy and helped it weather both the land boom collapse of the mid 1920s and the Depression of the 1930s.
During the years before World War II, the county's population remained fairly constant, at nearly 40,000, but Gainesville rose to almost 14,000, nearly four times its size in 1900. These years witnessed the construction of a magnificent new post office, the White House Hotel, Trinity Church, the Seagle Building and a public hospital. In 1928, William Reuben Thomas opened the Thomas Hotel, which served as the town's social and cultural center for the next 30 years.
World War II deeply affected both the county and Gainesville, as thousands of men and women from the county and the university served in the war. Some died as heroes, including Milton Lewis; some became war aces, including John Alison; and one, Colonel Paul Tibbets, piloted the plane which dropped the first atomic bomb on Hiroshima.