Charles Lee Smith was born on August 29, 1865, in Wilton, N.C., to Dr. Louis Turner Smith, a physician, and Nannie Green Howell Smith. In 1875, the Smith family moved to Durham where father Smith gained a large practice as physician and surgeon and established business interests. Charles Lee entered the Buchanan School, of which Luther T. Buchanan, a graduate of Wake Forest College, was principal. Charles D McIver, a recent graduate of the University of North Carolina, was one of his teachers.

In January 1882, Smith entered Wake Forest College as a sophomore with the intention was to study law. Joining the Philomathesian Literary Society, young Smith threw himself into its activities to obtain the maximum practice in speaking. The prominence which he won in the Society helped turn him from the law. In recognition of his skill in the use of language, the Society in 1883 elected him as the senior editor of The Wake Forest Student, the literary magazine established in January 1882; thus he became co-editor of its third volume.

After graduating from Wake Forest College in June 1884, Smith taught at the Raleigh Male Academy, was a member of the editorial staff at the Biblical Recorder and became a student in the Department of History and Politics in the Johns Hopkins University in Baltimore, Maryland. His studies continued in 1888 in Germany at the University of Halle. Smith then returned to Johns Hopkins, where he earned his doctorate in 1889.

Continuing his work in academia, Smith stayed at Hopkins as instructor in history and lecturer in sociology. In summer 1905, the Mercer University, Baptist College of Georgia, Board of Trustees unanimously elected Smith president of that institution. Smith had an ambitious program for Mercer, but before the first scholastic year was out, it was evident that Smith was too far ahead of his constituency. He resigned after one year. By 1915, he had become the president of Edwards and Broughton, a Raleigh printing and publishing house with a superior reputation since 1871. He remained in the position for 33 years, and many Smiths joined the business as well.

In 1911, he was elected a trustee of the University of North Carolina, and in the following year he was chosen by the Board to serve on the executive committee as successor of Charles B. Aycock and later on the building committee; he continued to serve until 1932. Wake Forest College conferred on him the degree of LL. D. in 1906, and in 1941 when a chapter of Phi Beta Kappa was established at the college, he was one of the twenty alumni initiated as foundation members. Soon after returning to N.C., he led in the raising funds of Wake County alumni of Wake Forest and in raising funds for a Wake County scholarship.

In 1922, he began making annual journeys abroad. On these trips, which often lasted three to six months, he acted alternately as a political scientist studying other peoples and talking with their leaders, and a bibliophile collecting books and visiting libraries and book dealers. He traveled to Europe fifteen or more times, to Asia three times, and to Africa three times. In 1924 he took a trip around the world.

Smith and Miss Sallie Lindsay Jones were married on October 24, 1889, in High Point, N.C. Together they had three sons and one daughter. After Sallie's death in 1931, Smith was married to Celeste Henkel in 1934 and then, following Celeste's death, Cora Vaughn. Smith died July 14, 1951, and is buried in Raleigh's Oakwood Cemetery.

When Smith presented his library to Wake Forest College in 1941, he stipulated that it be maintained intact as a separate unit so that "future generations can have a realistic example of a comprehensive private library of the first half of the twentieth century." Oscar T. Smith, Charles Lee Smith's brother and fellow Wake Forest alumnus (1888), also left a trust to continue building on and preserving his brother's donated collection.