Catharine was born in 1824 in Corydon, Indiana. Her father was Samuel Merrill, an early leading citizen of the state. She studied literature in Germany and taught in Cleveland, Ohio and Crawfordsville, Indiana. In 1867 she was appointed as the Demia Butler Professor of English at North Western Christian University, now known as Butler University. This was the first endowed chair at an American university designated for a female professor, and it made Merrill only the second female professor in the country (she was preceded by Maria Mitchell at Vassar College). She was the first to use the lecture method for a subject other than science.
During the Civil War she served as a nurse in Kentucky. After the war she was asked by Indiana Governor Oliver P. Morton to write a history of Indiana's solidiers in the war. It was published anonymously as The Soldier of Indiana in the War for the Union (2 vol, 1866, 1869). She also published The Man Shakespeare and Other Essays in 1902.
She met John Muir when he lived in Indianapolis in 1866-1867, and helped take care of him when he temporarily lost his vision in an accident. This began a lifelong friendship, and Muir wrote a tribute to Catharine after she died entitled Words from an Old Friend.
Catharine retired in 1883 and died in 1900.
In 1885 The Catharine Merrill Club was founded in her honor.
- Muir, John. "Words from an Old Friend (Tribute to Catharine Merrill)". Sierra Club. Retrieved 2012-10-19.
- "Catharine Merrill". Sierra Club. Retrieved 2012-10-19.
- "Merrill-Graydon Family Papers, 1836-1930 (Bulk 1890-1920), Collection Guide". Indiana Historical Society. Retrieved 2012-10-19.