He served in the capacity of a brigadier surgeon in the American Civil War, later as a member of General Ulysses S. Grant's staff.

Surgeon General William Alexander Hammond made him the first curator of the National Museum of Health and Medicine.

In 1866, he married Sarah Ward (who also posed for Eakins), with whom he would father six children.

Brinton succeeded Dr. Samuel D. Gross (who was featured in Thomas Eakins' The Gross Clinic), in the chair of surgery at Jefferson College, and also served as the chairman of the Mütter Museum Committee of the College of Physicians of Philadelphia.

He also founded the Philadelphia Pathological Society, and served as the first curator of the National Museum of Health and Medicine in Washington, D.C.