Clyde was born near Laredo, Missouri, the son of farmer James W. Tolson and his wife. His father moved his family to Cedar Rapids to work for the railroad, and Clyde graduated from Cedar Rapids Business College.

He went to business college and at the age of eighteen he moved to Washington where he found work as a clerk in the War Department. In an attempt to improve his future prospects, Tolson attended George Washington University.

Clyde moved to Washington, D.C., in 1918, when war was on everyone's mind. There he joined the War Department and became the confidential clerk to three successive secretaries of war. He attended night classes at George Washington University, receiving a bachelor's degree in 1925 and a law degree in 1927.

When Clyde obtained his law degree, he applied to join the Federal Bureau of Investigation (FBI) but was rejected. He tried again the following year and this time his photograph and application form was seen by J. Edgar Hoover, assistant director of the FBI.

Hoover hired him in 1928. Within three years, Clyde moved up the ranks to assistant director, a title that was later changed to associate director. He took care of all personnel and disciplinary matters, rather than crime-fighting, and was responsible for making sure Hoover's policies were carried out.

Clyde became Hoover's confidant, closest companion and alter ego, and for the next forty years they were constant companions. In the FBI the couple were known as "J. Edna and Mother Tolson". However, fellow homosexual, Truman Capote, preferred the names, "Johnny and Clyde".

Mafia boss, Meyer Lansky, obtained photographic evidence of Hoover's homosexuality and was able to use this to stop the Federal Bureau of Investigation from looking too closely into his own criminal activities.

The two bachelors were close on the job and off - eating, traveling, vacationing and attending social engagements together for over 40 years. They were often seen at the horse races or at the Stork Club and Yankee Stadium during trips to New York. When Clyde's parents died, Hoover returned to Iowa with him for their funerals.

Sometimes journalists hinted at the relationship the two men were having. Time Magazine ran one article where it stated that "Hoover is seldom seen without a male companion, most frequently solemn-faced Clyde Tolson". When this happened the journalist concerned would find himself being investigated by the Federal Bureau of Investigation.

When J. Edgar Hoover died in May, 1972, he left virtually the whole of his estate to his long-time companion, and Clyde moved into his home. He also took control of Hoover's considerable secret files. Clyde retired from the FBI two weeks after Hoover's death, and according to his friends, that the only time he left the house was to visit Hoover's grave.

When Clyde died in April, 1975, it was reported that the FBI agents arrived at his house and removed all these documents. Clyde Tolson is buried with Hoover at the Congressional Cemetery in Washington.