Eliza McCardle was the daughter of shoemaker John McCardle and Sarah Phillips. Born on October 4, 1810, in Leesburg, Tennessee, she was an only child. Her father died when she was very young. Nonetheless, she had a good education and in fact, when she married Andrew Johnson at the age of sixteen, she helped him with his reading and writing skills. The pair were married on May 17, 1827 in Greeneville, Tennesse. Together, Eliza and Andrew Johnson had three sons and two daughters: Martha, Charles, Mary, Robert, and Andrew Johnson Jr.

Eliza was an invalid after 1865 and while first lady she stayed in her room on the second floor of the White House. Their daughter Martha Patterson took over the social duties of being first lady with Eliza appearing publicly only twice. She died in 1876, six months after her husband's death.