Mary Anna Randolph Custis Lee (October 1, 1808 – November 5, 1873) was the wife of Confederate General Robert E. Lee.

In 1759, 27-year-old George Washington married rich widow Martha Parke Custis, who had two children, six-year-old John Parke Custis and four-year-old Martha Parke Custis. John died while serving as an aide to his stepfather during the Revolutionary War, leaving four young children. General Washington adopted two of the children, and they lived with him and their grandmother at Mount Vernon, their plantation in Virginia. Washington, childless himself, signed his letters to his adopted son, George Washington Parke Custis, as "your papa." Custis lived at Mount Vernon for 20 years and was close to Washington in his old age. Washington died in 1799; upon the 1802 death of Custis's grandmother, Mount Vernon reverted to the Washington family, and Custis built Arlington on the Potomac River's southern shore as his residence. Of the four children he had with his wife, Mary Lee Fitzhugh, the only one to survive infancy was Mary Anne Randolph Custis.

Mary was diminutive and vivacious and had known Robert E. Lee from childhood. Among her other suitors was Sam Houston. The pair were married at her parents' home, Arlington House, June 30, 1831 and had seven children, three sons and four daughters: George Washington Custis, William H. Fitzhugh, Robert Edward, Mary, Agnes, Annie, and Mildred.

Mary inherited Arlington House from her father, and the estate became the couple's home whenever they were in the area. Mary was a gracious hostess and enjoyed frequent visitors. She was a painter, like her father, and painted many landscapes, some of which are still on view at the house. She loved roses and grew 11 varieties. She was deeply religious and attended Episcopal services when there was one near the army post. In Arlington, Virginia, the Lees attended the Christ Episcopal Church in Alexandria, the church she and Robert had attended in childhood.

Mary taught her slave women to read and write and was an advocate of eventual emancipation. She suffered from rheumatoid arthritis, and this became increasingly debilitating with advancing age. By 1861, she was confined to a wheelchair.

With the advent of the American Civil War, Lee and their sons were called to service in Virginia while Mary delayed evacuating Arlington House until May 15, 1861. Early that month, Lee wrote to Mary Anna saying:

"War is inevitable, and there is no telling when it will burst around you . . . You have to move and make arrangements to go to some point of safety which you must select. The Mount Vernon plate and pictures ought to be secured. Keep quiet while you remain, and in your preparations . . . May God keep and preserve you and have mercy on all our people."

Mary and her daughters moved between the several family plantations until they finally settled in Richmond, Virginia for the bulk of the war.

After the war, she accompanied her husband to Lexington, Virginia, where he became president of the Washington College, later renamed Washington and Lee University. She was able to visit her beloved Arlington House once more before her death, but she was unable to leave the carriage. She hardly recognized it except for a few old oaks and some of the trees she and Robert had planted. Mary died at the age of 66 and is buried next to her husband in the Lee family crypt at Lee Chapel on the campus of Washington and Lee.