Dr. Benjamin Rush was born on December 24, 1745, in Byberry Township, Pennsylvania. He was fourth of seven children for John and Susanna Rush, and he began his education at the age of eight and attended West Nottingham Academy in Rising Sun, Maryland. At the age of 15, Rush graduated with a B.A. from the College of Philadelphia (now the University of Pennsylvania), after which he spent four years under the tutelage of Dr. John Redman, the leading physician in Philadelphia at the time, while continuing to attend lectures at the College of Philadelphia.

Upon finishing his studies in July 1766, he decided to attend the University of Edinburgh in order to obtain his medical degree. In 1768, he graduated from the University of Edinburgh and moved to London to train and attend lectures at St. Thomas Hospital. By autumn of 1768, he had returned to the Thirteen Colonies and begun his medical practice. After just two months in Philadelphia, he was given the professorship of chemistry at the College of Philadelphia—the first such professorship given in the Colonies. During this time, he wrote prolifically, became a member of the American Philosophical Society, and also wrote the first American textbook about chemistry.

Rush was the surgeon for the Pennsylvania Navy from 1775 to 1776. It was at this time that he wrote Directors for Preserving the Health of Soldiers. This text was used by the United States Military Medical Department up to the time of the Civil War. Rush was offered a seat in the General Congress of 1775, but he declined. However, he was one of the Sons of Liberty who rode out to greet the delegates from New England for their arrival at the First Continental Congress. In July 1776 he became a leader in the movement for independence when he was elected to the Provincial Conference. A month later, he became a member of the Continental Congress when Robert Morris and John Dickinson withdrew from their seats. Though it was too late to have been present for the adoption of the Declaration, he was present for the signing on August 2, 1776.

In 1777, Rush was made the Surgeon General of Military Hospitals for the Middle Departments, and he refused pay for this position. Upon discovering that the army medical service was in very poor condition, he accused Dr. William Shippen of maladministration and lodged a complaint with General Washington. General Washington turned the report over to Congress, which decided in Dr. Shippen's favor, after which Rush angrily resigned from his post on January 3, 1778. Doubting the abilities of General Washington after several military defeats, Rush wrote an anonymous letter to the Virginia Governor, Patrick Henry, suggesting that General Horatio Gates on Conway replace General Washington. Governor Henry sent the letter on to General Washington, who recognized Rush's handwriting, which led to the end of Rush's military medical career and put a temporary halt to his political career as well. Rush returned to his private medical practice in Philadelphia and began lecturing at the new University of Pennsylvania in 1780.

In 1783, he became a member of the staff of the Pennsylvania Hospital, founded in 1751. There, he established the first free dispensary in the United States, which provided free clinical treatment. He remained on staff until his death. In 1783, he helped the Presbyterians found Dickinson College, where he also served as a trustee. In 1787, as a member of the Pennsylvania Convention, he ratified the United States Constitution and also framed a Constitution for Pennsylvania. Benjamin Rush was the only person to leave a record of the yellow fever epidemic of 1793 in Philadelphia. Unfortunately, he failed to keep accurate records of his cases. The other physicians fled the city when all known remedies and the best medical treatments failed. Rush remained to treat the sick, and he suffered a severe attack of yellow fever himself.

In 1797, another yellow fever epidemic swept Philadelphia. This time, however, physicians noted that more patients died when they were treated rather than when they were left alone. They argued that the use of mercury and bloodletting, two of Rush's most common practices, were responsible for this skewed death rate. It was in this same year that John Adams appointed Rush as the treasurer of the United States Mint and later the Pennsylvania Mint struck two medals in his honor in 1808. Rush was an advocate of women's education and of the abolition of slavery. He became a trustee of the Young Ladies' Academy in Philadelphia in 1786. In 1803, he became the president of the Pennsylvania Society for the Abolition of Slavery. Rush had 13 children with his wife Julia Stackton. He was survived by nine of his children when a typhus epidemic claimed his life at the age of 67 on April 19, 1813, in Philadelphia, Pennsylvania.