Anna Tuthill Harrison (née Symmes; July 25, 1775 – February 25, 1864) was the first lady of the United States in 1841 as the wife of President William Henry Harrison. She served in the role for only one month, as her husband contracted pneumonia and died shortly after his term began. Their son John Scott Harrison was the father of President Benjamin Harrison. She never entered the White House during her tenure as first lady, remaining the only presidential wife to never visit the capital during her husband's presidency. At age 65 when her husband's presidential term began, Harrison was the oldest woman ever to assume the role of first lady, a record held until Jill Biden became first lady at age 69 in 2021. She also has the distinction of holding the title for the shortest length of time, and the first first lady to be widowed while holding the title. Harrison was the only First Lady of the United States to have been the wife of one U.S. President and the grandmother of another U.S. President.

Anna was raised by her grandparents on Long Island and given an education better than any other first lady had yet received. She married military officer William Henry Harrison against her father's wishes in 1795, and she raised their family of ten children in the frontier of Ohio and Indiana while William pursued a political career. Eight of Anna's ten children died in her lifetime, causing her to become more deeply involved in her Presbyterian faith. She became first lady when William became president in 1841, though she did not attend his inauguration. William died while Anna was preparing to travel to Washington, D.C., only one month into his term. Anna lived the remainder of her life in Ohio, first in their family log cabin, and then with her only surviving son, John. Her short tenure as first lady, her absence from the White House, and the destruction of her personal papers in a fire have caused her to be overlooked by historians, and her life has been the subject of relatively little scholarly analysis.

Anna Tuthill Symmes was born on July 25, 1775, in Morristown, New Jersey, as the second child of Anna Tuthill and John Cleves Symmes. Her father was an associate justice on the Supreme Court of New Jersey. Her mother died on her first birthday, leaving her father to raise her alone. When the American Revolutionary War began, John was a colonel in the Continental Army. To ensure his daughter's safety, he assumed the guise of a British soldier and transported her to Long Island via horseback. Here she was raised by her maternal grandparents. One rumor suggested that John carried two bags: one with Anna, and one with turnips that he showed to any soldiers who questioned him, claiming that he was delivering them to the British commander.

As a child, Anna first attended Clinton Academy in East Hampton and then the private school of Isabella Graham in New York City. Her education was religious in nature, as her grandparents raised her to be a Presbyterian. Once the war ended in 1783, Anna's father paid her a brief visit in New York before relocating to the Northwest Territory. She reunited with her father in 1794 at the age of 19 when she moved to the Northwest Territory to live with him in the town that he had established there: North Bend, Ohio. Also present was her stepmother, Susannah Livingston, with whom Anna got along well.

Symmes met William Henry Harrison during a visit to Lexington, Kentucky, to see her sister Maria. Despite her father's disapproval, she began a courtship with him. Her father disapproved of the courtship because of Harrison's military career. His experience with the soldiers of the Northwest Territory convinced him that they were little more than criminals, and he feared that Harrison's lack of experience in any other field would make it difficult to provide for a family.

Symmes and Harrison decided to elope while her father was away on business. They were married on November 25, 1795, with Dr. Stephen Wood presiding. The ceremony may have been in the home of the presiding minister or at the home of Anna's father; historians disagree on the exact location. Anna's father was displeased, and weeks went by before he finally spoke to his new son-in-law, demanding to know how he would support a family with Anna. William responded that he would use his sword. John's animosity toward William did not last. He eventually campaigned on his behalf and named him an executor of his estate.

Anna accompanied William when he returned to the nearby Fort Washington where he was stationed. She lived the traditional life of an army wife, including the associated travel with her husband. In 1798, William resigned from the army, purchased land in North Bend, and built a log cabin for their home. At this point they had their first child, who had been born in 1796. They eventually had ten children together over a period of 18 years. Eight of them preceded Anna in death.

After William was elected to the House of Representatives in 1799, the family moved to Philadelphia, which was the capital of the United States at the time. Besides Philadelphia, they also spent time in Richmond, Virginia, to see William's family. It was here that Anna had their third child in 1800. They moved to Vincennes, Indiana, later that year when William was appointed territorial governor of Indiana. After four years in Vincennes, William built Grouseland, a brick house for the Harrisons that also served as a popular location for the territory's social events. Attacks on families by Native American soldiers sometimes occurred in the region, and the children were regularly forced to hide inside the home, which was built to be readily defensible. A Methodist minister lived with the Harrisons in Grouseland, and he guarded the house during attacks. While living in Vincennes, Anna sought whatever newspapers and journals she could, reading about various political topics. She felt lonely in Vincennes because of the distance from her extended family; the opportunity to meet visiting national figures provided little consolation. She had five more children during her time in Indiana.