Richard Beverly Cole was born in Manchester, Virginia on August 12, 1829. He began his medical studies at the age of sixteen when he became an assistant to Dr. Benjamin Dudley of Lexington, Kentucky. After a few months of this apprenticeship, he enrolled in the Medical Department of Transylvania University (now the University of Louisville). After a year he transferred to Jefferson Medical College in Philadelphia, receiving his M.D. in March of 1849. In May of 1849 a cholera epidemic broke out in Philadelphia; Dr. Cole was made physician in chief of the Pine Street Cholera Hospital, living and working within the walls of this temporary institution until the epidemic subsided in August, shortly after his twentieth birthday. He continued in general practice in Philadelphia until 1852, when he emigrated to California.

He established an office in Little's Drug Store at 137 Montgomery Street in San Francisco, first as a surgeon and later specializing in gynecology and obstetrics. This was a historically eventful period in San Francisco, and Cole played a part in much of that history. On May 14, 1856, Cole was one of the many physicians in attendance when James King of William --a personal friend of Cole's --was fatally shot by James Casey. Following King's death, Cole claimed that the physicians in charge of the case were guilty of malpractice. The claim was an issue in the 1858 trial of Judge Edward McGowan; McGowan was acquitted, but Cole had earned the enmity of H. H. Toland (the two physicians had given opposing testimony). Also during this period Cole functioned as surgeon to the second Committee of Vigilance; in this capacity on June 21, 1856, he saved the life of Sterling Hopkins, a marshall of the Committee of Vigilance who had been stabbed in the throat by Judge David Terry. This case may have been the partial basis for Cole's having been credited with being the first practitioner to ligate the common carotid and femoral vessels. In 1858, as chairman of the Committee on Obstetrics and Diseases of Women of the California State Medical Society, Cole presented a report to a meeting of the society that included "extensive comment on the conduct and morals of the girls and women of California."

Cole made more enemies with such injudicious remarks, and sustained some damage to his professional reputation. Despite this, in 1859 Cole was invited by Elias Samuel Cooper to join the faculty of the Medical Department of the University of the Pacific, the first medical school in California. Cole was professor of obstetrics and gynecology and also served as dean of the school, which unfortunately collapsed within two years. This period also saw the rise of the medical school established by Cole's rival H. H. Toland. It has been said that this loss to Cole's reputation, and not just his poor health or even his sympathy to the Confederate cause, was the reason he and his wife spent much of the Civil War years in Europe. During this extended stay in Europe, Cole visited medical institutions in England, Ireland, Scotland, France and Germany and obtained numerous diplomas, fellowships and memberships. He returned to the United States in the spring of 1865 to find that the faculty of the defunct Medical Department of the University of the Pacific, including Samuel Cooper's nephew Levi Cooper Lane, now was part of the staff of Toland Medical College.

In 1867 Cole became a member of the Outside Lands Committee of the San Francisco Board of Supervisors; in this capacity he interested the city in 1000 acres of land at the city's westerm edge which eventually became Golden Gate Park. The following year San Francisco suffered an epidemic of smallpox, and Cole was appointed chairman of the Board of Supervisors' Hospital Committee. Coming to notice by his outstanding services in the course of the epidemic, he was appointed Surgeon General of the State of California, a position he held for four years.

In 1870 Toland conceded to Cole's renewed prominence and invited him to join the faculty of the Toland Medical College as dean of the school (1871-1881) and professor of gynecology (1870-1901). Cole's first important suggestion involved the school's affiliation with the University of California; he conciliated negotiations between Toland and the regents, and the affiliation took place in 1873. Cole became president of the faculty in 1876. From 1873 to 1876 he was editor of the Western Lancet. In 1895 he was elected president of the American Medical Association. In March of 1897 Cole oversaw the laying of the cornerstone for the new medical buildings on Parnassus Avenue. He continued his involvement with medical agencies of local government, and had begun a term as coroner when he died on January 15, 1901.