Parran was born on September 28, 1892 and raised near St. Leonard's, Maryland, on his family's tobacco farm. He was tutored at home by a relative and attended St. John's College in Annapolis, Maryland on scholarship (1911, A.B.; 1915, A.M.). Finances influenced his decision to attend Georgetown (1915, M.D.) and to follow with an internship at Sibley Memorial Hospital in Washington, DC. A lifelong interest in research was sparked during medical school. He volunteered at a health laboratory operated by the District of Columbia, under Dr. Joseph J. Kinyoun, founder of Public Healt Service's Hygienic Laboratory (renamed the National Institute of Health in 1930). Kinyoun recruited Parran to join a field team of young physicians under PHS's Dr. Leslie L. Lumsden, building privies and surveying conditions in the southern United States. In March 1917, Parran reported to Okmulgee, Oklahoma, for the first of many assignments in rural sanitation.

After receiving an Assistant Surgeon's commission in September 1917, Parran continued on assignments in rural health services administration, sanitation, and the control of communicable diseases; between field assignments, Parran tasted life as an administrator in Washington, DC. In October 1923, he joined a group of young medical officers who attended 6 months of coursework at the Hygienic Laboratory, receiving the practical equivalent of a master's degree in public health. Parran's first leadership position was as Chief of PHS's Division of Venereal Diseases (September 1926), a program begun during World War I. Parran worked to sway public sentiment away from moral condemnation of venereal diseases and toward consideration of syphilis as a medical condition and threat to public health.

His talents in rural health administration would soon lead him temporarily in a new direction. A reform-minded Governor Franklin Delano Roosevelt requested that Parran be loaned to the State of New York, where in April 1930 Parran took up his post as state health commissioner. His primary task was chairing a Special Health Commission whose recommendations (1932) provided a framework to bolster county health departments in the face of Great Depression-Era needs. Few of the Commission's recommendations were enacted. Parran's work on syphilis achieved more success. The Columbia Broadcasting System inadvertently launched his campaign after radio executives censored the phrase "syphilis control" from a talk, leading Parran to cancel his appearance. Newspapers across the United States reprinted the censored speech.

Parran became active in New Deal politics in New York and entered national politics as well. In 1934 his former supervisor-now President of the United States-Roosevelt appointed Parran to the Committee on Economic Security, which drafted the Social Security Act of 1935; Title 6 authorized millions for public health departments and for biomedical research. And following the close of Surgeon General Hugh S. Cumming's term, President Roosevelt appointed Parran as Surgeon General of the United States; he was sworn in on April 6, 1936.

Parran's syphilis control campaign was in full swing by the fall of 1936. Title 6 funds supported efforts to identify and treat syphilis, the National Venereal Disease Control Act of 1938 made funds available for rapid treatment centers that employed the new sulfa drugs and, later, penicillin. During 1937 his book about syphilis, Shadow on the Land, was published and very well received.

In addition to syphilis control, Surgeon General Parran left his mark on the scope and structure of public health, both at home and abroad. World War II brought quick expansion and new opportunities for expanded duties. In response Parran and his deputies rewrote the statutes underlying PHS operations-the Public Health Service Acts of 1943 and 1944-establishing a four-bureau structure that would remain in place through 1967, and deftly arranged for the transfer of wartime research contracts from the Office of Scientific Research and Development, creating an extramural grants program for NIH. Parran also served as a mentor to a generation of Public Health Service Commissioned Corps physicians, to whom he gave the leeway to create new institutions and programs in the areas of clinical research into cancer and other conditions, mental health, tuberculosis control, prevention of malaria and other communicable diseases, construction of nonprofit hospitals, and international health. Parran's leadership role in international health affairs dated back to the 1930s with the Rockefeller Foundation and the Pan American Health Organization. Parran chaired the International Health Conference where the World Health Organization (WHO)'s draft constitution was adopted (1946) and led subsequent U.S. delegations.

Parran was an early and committed advocate of national health insurance, shielding PHS from direct conflict with those who opposed insurance by tempering his public advocacy with a focus on creating a regionally organized health services infrastructure to precede Federal dollars for care. The Hospital Survey and Construction Act of 1946 (Hill-Burton) was a signal step in this direction. Nevertheless, Parran was attacked by American Medical Association editorialist Morris Fishbein for supporting President Truman's proposed national insurance program. Truman's decision not to reappoint Parran in the spring of 1948 may have been an outcome of public disputes over this issue.

On October 1, 1948, Surgeon General Parran retired from PHS to begin a career in academic administration, to serve as the first dean of the new public health school at the University of Pittsburgh. Parran made Pittsburgh, Pennsylvania a proving ground for ideas developed during his tenure at PHS, recruiting the school's first generation of senior faculty and bringing his deputy surgeon general and veteran international health administrator, Dr. James A. Crabtree, who succeeded him as dean in 1958. Beyond his tenure as Surgeon General, Parran remained prominent in international health, active in the Pan American Sanitary Organization and in Rockefeller Foundation programs. On retiring from Pittsburgh in 1958, Dr. Parran became president of the Avalon Foundation, affiliated with the Mellon family, and became active in the A.W. Mellon Educational and Charitable Trust, where he had served as a trustee since 1955. He continued his work in philanthropy and public health until his death on February 16, 1968, in Pittsburgh, Pennsylvania.