In 1885, Woodrow Wilson married Ellen Louise Axton, the daughter of a Presbyterian minister. Ellen was a painter and actually had a studio set up for her in the White House. Together, the Wilsons had three daughters, two of whom were married in the White House. Ellen also worked to help alleviate the living conditions for African Americans and for the poor in Washington, D.C. She died on August 6, 1914 of Bright's disease. She was the only first lady to die in the White House.

After Ellen's death, Wilson's cousin took on the traditional first lady's duties. It was she who introduced Wilson to his next wife, Edith Bolling Galt. A little more than a year after the death of his first wife, Wilson married Edith on December 18, 1915.

In 1919, Edith Wilson basically took control of the presidency after her husband suffered a stroke. She only took items she considered important to the president. She was criticized for this, but she always claimed that she made no decisions herself except for deciding what the president should or should not see. But in the end, it is not known how much power she truly wielded. Edith died on December 28, 1961.