Born in Putnam, Connecticut, Warner dreamed of being a famous author from the age of five. Her favorite book was Alice's Adventures in Wonderland. Being in a musical family, she was almost predisposed to play in instrument; in her case, she chose the cello, and her father bought her a cello kit at a young age. However, because of her frequent illness, Warner never finished high school. After leaving in her sophomore year, she learned from a tutor and finished her secondary education.

In 1918, while she was teaching Sunday School, Warner was called to teach first grade, mainly because male teachers were being called to serve in World War I. She thought up the Boxcar Children while at home, sick. The stories were perfect for children, especially the majority (at least in her class) who did not speak very good English. She was criticized for displaying children with little parental supervision; her critics thought that that would encourage child rebellion. Her response was, however, that the children liked it for that very reason.

The series was originally published by Scott Foresman, starting in 1942. Today, Albert Whitman & Company publishes the extremely popular series of 19 stories. Other authors have contributed to the series, adding approximately 30 books to the series. In her later life, before dying in 1979, Warner became a volunteer for the American Red Cross and assisted other charitable organizations.