Leslie Cheek was born in Nashville, TN in 1908. He studied art at Harvard University and architecture at Yale and Columbia. He headed the department of fine arts at the College of William and Mary 1937-39, where he was instrumental in getting an honorary award given to Georgia O'Keeffe by the college in 1938 and Frank Lloyd Wright.

In 1939, he married Mary Tyler Freeman (1917- 2005), the daughter of the Pulitzer Prize-winning biographer of George Washington, Douglas Southall Freeman. That same year he joined the Baltimore Museum of Fine Art as its director, where he found Adelyn Breeskin (q.v.) of its prints department already assembling an outstanding collection. Cheek worked actively with various Works Progress Administration (WPA) artist's projects. He resigned from the Museum in 1942 to join the army corps of engineers in World War II.

After the war, he succeeded Thomas C. Colt, Jr as the second director of the Virginia Museum of Fine Arts in 1948 (the museum itself was founded in 1936). During his tenure at Virginia, he persuaded the General Assembly to finance the Museum as the state's official art museum. In 1953, Cheek developed a "mobile art program" to bring exhibitions to more remote parts of Virginia. The project, Artmobile I, was a success. In 1955, the Virginia Museum Theater opened to integrate the performing arts with the gallery. He retired from the Museum in 1968. The following year the Cheeks began a mountaintop compound they named Skylark on a former farm along the Blue Ridge Parkway. In 1977, they donated it to Washington & Lee University which is today that university's conference center. Cheek suffered a series of strokes at his home in Richmond and died in 1992. His personal papers, 1981-1994, are held by the Museum of Modern Art, New York, and 1940-1983 by the Archives of American Art, Washington, DC. The Cheekwood Botanical Garden and Museum of Art, Nashville, TN, the ancestral home of Cheek, is now a public art museum, built upon the collection of the former Nashville Museum of Art.