The early campus grew building by building across the Oklahoma plain. Williams Hall, constructed in 1900 as the first electrified building on campus, was nicknamed the 'Castle of the Prairies' for its turreted architecture. It survived until 1969. A barn serving the agricultural experiment station gave way to fire in 1922, but its reservoir pond, enlarged in 1928 and 1943, became the beloved Theta Pond that remains a campus landmark. Morrill Hall, completed in 1906, was gutted by fire in 1914 but its exterior survived, and the interior was rebuilt. These early years set a pattern: the campus kept rebuilding itself, each time more ambitiously than before.

President Henry G. Bennett transformed Oklahoma A&M from 1928 to 1950, developing the strategic campus plan adopted in 1937 that guided construction for more than fifty years. He established the predominant Georgian architecture that still defines the campus and envisioned a centrally located library as its focal point. That became the Edmon Low Library, which opened in 1953. The Student Union, which opened in 1950, grew through subsequent additions into one of the largest student union buildings in the world. Bennett's ambitions extended far beyond Stillwater. Appointed in 1950 as the first director of President Truman's Point Four Program, he helped Oklahoma A&M establish Jimma University and Haramaya University in Ethiopia. Emperor Haile Selassie visited Stillwater in 1954, the first foreign head of state to set foot in Oklahoma.

Oklahoma State's athletic identity is forged in the wrestling room. The Cowboys' 34 NCAA team wrestling titles are the most ever won by any school in any single sport. They have produced 143 individual national champions, including Pat Smith, the sport's first-ever four-time champion. Beyond the mat, OSU athletes have earned 34 Olympic medals, including 21 gold. The football program claimed a national championship in 1945 and produced Barry Sanders, the 1988 Heisman Trophy winner who set the single-season rushing record. Men's basketball made history as the first Division I program to win back-to-back national championships in 1945 and 1946. The annual Homecoming celebration, dating to 1913, draws over 70,000 participants and bills itself as 'America's Greatest Homecoming Celebration.'

On May 15, 1957, Oklahoma A&M became Oklahoma State University, reflecting the broadened scope of a curriculum that had grown well beyond agriculture. The university has produced 48 Fulbright Scholars, an astronaut, and a billionaire in T. Boone Pickens, whose donations exceeding $500 million reshaped the campus. Notable alumni span a remarkable range: country legend Garth Brooks, Ed Roberts who is credited as the father of the personal computer, legal scholar Anita Hill, and actor James Marsden. OSU also established the nation's first and currently only tribally affiliated medical school, in partnership with the Cherokee Nation in Tahlequah. The university spent $226.5 million on research and development in 2023, a testament to the distance traveled from that borrowed church in 1891.