Born as a free person of color in Charles Town, Virginia, now West Virginia (not Charleston, West Virginia), and raised in Chambersburg and Pittsburgh, Pennsylvania, Delany trained as a physician's assistant. During the cholera epidemics of 1833 and 1854 in Pittsburgh, Delany treated patients, even though many doctors and residents fled the city out of fear of contamination. In this period, people did not know how the disease was transmitted.
Delany traveled in the South in 1839 to observe slavery firsthand. Beginning in 1847, he worked alongside Frederick Douglass in Rochester, New York to publish the North Star. In 1850, Delany was one of the first three black men admitted to Harvard Medical School, but all were dismissed after a few weeks because of widespread protests by white students.
Delany dreamed of establishing a settlement in West Africa. He visited Liberia, a United States colony founded by the American Colonization Society, and lived in Canada for several years, but when the American Civil War began, he returned to the United States. When the United States Colored Troops were created in 1863, he recruited for them. Commissioned as a major in February 1865, Delany became the first African-American field grade officer in the United States Army.

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