She was born at Monticello, near Charlottesville, Virginia.
She married Thomas Mann Randolph Jr., who served as a politician at the federal and state levels and was elected a governor of Virginia (1819–1822), making her the First Lady of Virginia.
They had twelve children together.
When her widowed father was President, she sometimes lived with him at the White House, serving as his hostess and informal First Lady.
Martha was very close to her father in his old age.
She was the only one of his acknowledged children to survive past age 25.