Elizabeth “Bess” Virginia Wallace was born on February 13, 1885. Her father, David Wallace, was a public official who committed suicide when she was eighteen. Bess grew up in Independence and was a childhood friend of Truman. She attended Miss Barstow's Finishing School in Kansas City. Truman and Bess did not start dating until 1913, and waited until after World War I to marry when he was thirty-five and she was thirty-four. They were wed on June 28, 1919. The Trumans had one daughter, Mary Margaret, a singer and a novelist, who wrote not only biographies of her parents, but also mysteries such as Murder in the White House and Murder at the Kennedy Center.

Truman defended his daughter against criticism. Once when a critic wrote of her singing that “Miss Truman … cannot sing very well [and] is flat a good deal of the time,” Truman responded, “It seems to me that you are a frustrated old man who wishes he could have been successful. When you write such poppy-cock … it shows conclusively that you're off the beam and at least four of your ulcers are at work.”

Bess Truman did not relish the role of first lady. While Truman was president, the White House was being completely refurbished — it had been discovered that the building was in danger of actually falling down — and so their family lived in the Blair House nearby. Bess spent as little time in Washington as possible, only living there during the yearly social season that comprises the warmer summer months. The rest of her time was spent in Independence.