Eastman was born on February 24, 1818, in Warrenton, Fauquier County, Virginia, to Thomas Henderson, a physician, and Anna Maria Truxtun, the daughter of Commodore Thomas Truxtun.
Truxtun was a hero during the United States' Quasi-War with France.
As she stated in her novel Aunt Phillis's Cabin (1852), Eastman was a descendant of the First Families of Virginia and had grown up in slaveholding society.
She grew up in the state but her family relocated to Washington, D.C., when her father was appointed as assistant surgeon general of the United States Army.
It is suggested that she received her education in Washington.

In 1835, she met and married Seth Eastman.
Seth, who previously had a Native American wife, was twenty-seven while Mary was seventeen.
He was a topographical engineering graduate from West Point and a distinguished painter.
He would later become the commander of the Confederate prisoner-of-war compound in New York, which was noted for having the highest mortality rate of any Union stockade.

By 1841, Eastman accompanied her husband when he assumed command of Fort Snelling (in what is now Minnesota), where he served until 1848.
During this period, Eastman learned the Sioux language to study and record the Sioux customs and lore.
Aside from their literary collaboration, she also helped her husband sell his paintings and secure a project with Henry Rowe Schoolcraft.

After the Eastmans returned to the East, they lived in Washington, D.C., where she worked to defend Southern slaveholding society before changing her position on slavery and becoming a Unionist.
Eastman died on February 24, 1887, in Washington, D.C.
Eastman was born on February 24, 1818, in Warrenton, Fauquier County, Virginia, to Thomas Henderson, a physician, and Anna Maria Truxtun, the daughter of Commodore Thomas Truxtun. Truxtun was a hero during the United States' Quasi-War with France. As she stated in her novel Aunt Phillis's Cabin (1852), Eastman was a descendant of the First Families of Virginia and had grown up in slaveholding society. She grew up in the state but her family relocated to Washington, D.C., when her father was appointed as assistant surgeon general of the United States Army. It is suggested that she received her education in Washington.
In 1835, she met and married Seth Eastman. Seth, who previously had a Native American wife, was twenty-seven while Mary was seventeen. He was a topographical engineering graduate from West Point and a distinguished painter. He would later become the commander of the Confederate prisoner-of-war compound in New York, which was noted for having the highest mortality rate of any Union stockade.
By 1841, Eastman accompanied her husband when he assumed command of Fort Snelling (in what is now Minnesota), where he served until 1848. During this period, Eastman learned the Sioux language to study and record the Sioux customs and lore. Aside from their literary collaboration, she also helped her husband sell his paintings and secure a project with Henry Rowe Schoolcraft.
After the Eastmans returned to the East, they lived in Washington, D.C., where she worked to defend Southern slaveholding society before changing her position on slavery and becoming a Unionist. Eastman died on February 24, 1887, in Washington, D.C.
Mary Henderson Eastman