The daughter of a college professor, Harrison was well-educated, and she expressed interest in art, music, and literature throughout her life.

She was in favor of women's rights, and she was an organizing member of the Daughters of the American Revolution, serving as its first President General.

[3] Her great-grandfather was the founder of the first Presbyterian church in the United States, and of the College of New Jersey, which was later renamed Princeton University.

[8]: 187  While Harrison advanced his legal career, Scott took a job as a music teacher in Carrollton, Kentucky, with Bethania Bishop Bennet.

[10] Caroline was severely overworked while in Kentucky, which negatively affected her health: as a result she and Benjamin wed sooner than originally planned.

[5]: 152  After their marriage, they stayed at the Harrison family home in North Bend, Ohio until Benjamin was admitted to the bar 1854, at which point they moved to Indianapolis.

She was also active in the community, joining the Indianapolis Orphans' Asylum board of managers in 1860 and holding the position until her death.

[11] Harrison experienced periods of loneliness and depression as her husband began his political career, for he was often away and their marriage was neglected.

It was finished in 1875, and gave Caroline experience in planning a home that would prove valuable when she became first lady years later.

[5]: 154  Her work as a family hostess grew significantly when her husband was chosen as the Republican candidate for the 1888 presidential election.

He ran a front porch campaign as was common at the time, bringing thousands of people through their home.

[1]: 151  She considered her domestic duties to be her primary responsibilities, expressing little interest in her role as White House hostess.

Harrison continued in her artistic pursuits while she was first lady, and she would mail ceramic milk sets to parents that named their children after the president.

[1]: 151  Harrison caused one major political controversy in 1889 when she accepted a seaside cottage from John Wanamaker as a gift, leading to accusations of bribery.

It was on her advice that her husband appointed Alice Sanger to the White House staff, the first woman to hold such a position.

[8]: 191  Harrison also organized educational programs in the White House for the wives and daughters of cabinet members, including ceramics and French classes.

[9]: 98  In 1890, Harrison was the first President General of the Daughters of the American Revolution, a woman's organization that celebrated the contributions of women during the founding of the United States.

[6]: 86–87  She took particular issue with the integration of the residential spaces and public offices, allowing visitors access to the family's quarters.

[8]: 189  She wished to entirely reconstruct the White House, even drawing plans with architect Frederick D. Owen, but Congress was unwilling to fund the project.

[14]: 273  Wooden structures in the state rooms were repainted ivory, and five layers of floorboards were replaced due to rot.

She oversaw the installation of electrical wiring over a period of four months, but the family and much of the staff were afraid to use the light switches.

[19] To address the rat problem, she released ferrets,[8]: 190 and she had the basement redone with concrete floors and tiled walls.

She traveled to spend the summer of 1892 in the Adirondack Mountains, as the air was considered healthful for tuberculosis patients.

Her condition was worsened by suspicions that her husband had begun a romantic relationship with her niece Mary Scott Dimmick.

Preliminary services were held in the East Room, then her body was returned to Indianapolis for the final funeral at her church and her burial at Crown Hill Cemetery.

[14]: 279–280  Early historical analysis of Harrison's performance as first lady often emphasized her role as a housekeeper, but her legacy has been reconsidered to include her advocacy for the arts, women's causes, and White House preservation.

[1]: 153  In her role as White House hostess, she is described as unsuccessful, being unable to maintain good relations with Washington society and lacking the grandeur associated with past first ladies.