In 1880, Upton's father was elected to Congress as a Republican, succeeding President James Garfield in the position. She went to Washington DC with her father where she met leaders in the suffrage movement like Susan B. Anthony.
Back in Ohio, Upton became a key organizer and the first president of the Suffrage Association of Warren. In 1894, Upton was elected as the treasurer of the National American Woman Suffrage Association (NAWSA), the leading national woman suffrage organization. She brought the headquarters of that organization home to Warren, Ohio, from 1903 to 1910.
After seeing the 19th amendment pass, Upton was elected Vice Chairman of the Executive Committee of the Republican National Committee. She attempted a run for congress in 1924, but was not successful. Her only electoral success was being the first woman elected to the Warren Board of Elections.
During the Great Depression, Upton and her husband lost all of their wealth. Upton spends her last days in California, in poverty. Harriet Taylor Upton died in Pasadena, California, on November 2, 1945. She was 91 years old at the time of her death.
The Harriet Taylor Upton House in Warren, Ohio, is a National Historic Landmark. It was almost lost when a group of local activists saved it from the wrecking ball. They were also able to work with a lawyer in California to have her cremains re-interred at her home in Warren.