Johnson significantly contributed to her husband's early career, providing him with an education and encouraging him to strengthen his oratory skills and seek office.

Though she only made two public appearances during her tenure as first lady, Johnson was a strong influence on her husband, and he would consult her regularly for advice.

Johnson returned to her home of Greeneville, Tennessee with her family after leaving the White House, living a quiet retirement.

[6]: 130 Eliza Johnson provided her husband much of his formal education,[2]: 117  though a common myth suggests that she even taught him to read and write.

Once they began having children, much of Johnson's time was spent tending to the household while her husband operated his tailor shop.

[7]: 231  As he attained higher political offices, Johnson avoided the social role associated with a politician's wife, instead tending to their home.

[7]: 232  As Johnson's children came of age, she enjoyed seeing her daughters seek husbands and start families of their own.

While initially ordered to vacate the entire region within 36 hours in May 1862, she replied "I cannot comply with the requirement", and she was granted an additional five months.

[5]: 204 Johnson eventually made the three week journey to Nashville, Tennessee, during which she was harassed and threatened for being the wife of a Unionist senator.

[1]: 109  This had a severe emotional effect on her; in one letter, her daughter Martha described her as "almost deranged" with worry that her husband would be assassinated as well.

[6]: 129  Johnson was not able to serve effectively as first lady due to her poor health, and she remained largely confined to her bedroom, leaving the social chores to her daughter Martha.

[1]: 109 Johnson would receive her husband's guests at the White House,[1]: 109  but she appeared publicly as first lady on only two occasions: a celebration for Queen Emma of Hawaii in 1866 and a children's ball for the president's sixtieth birthday in 1868.

[2]: 119–120  Each day, she would make her way through the White House residence, checking on her husband and the staff or spending time with her grandchildren.

[5]: 205  Johnson took up causes of her own, including a financial contribution to orphanages in Baltimore, Maryland,[3]: 198  and Charleston, South Carolina.

[3]: 198 Johnson did not have an active role in the politics of her husband's administration, though she gave him full support during his presidency, including during his impeachment.

[9]: 57 Johnson assisted the president with his speeches as she did in his previous political positions, and she worked to prevent the outbursts caused by his temper.

[3]: 199  Johnson lived a quieter life after ending her tenure as first lady, often spending her time with her children and grandchildren.

[2]: 120–121 Her health declined by the time her husband was elected to the United States Senate in 1875, and she moved in with her daughter Mary.

[7]: 234 Johnson was one of the least active first ladies, playing little role in the political or social aspects of the White House.

[3]: 200  Historians generally describe Johnson as unassuming and unable to fulfill the role of first lady, but also as a capable intellectual partner for her husband.