She was born in Philadelphia, Pennsylvania to a wealthy Religious Society of Friends (Quaker) family. After graduating from the Friends Select School in Philadelphia in 1879, she worked at home and on the family farm. During this time she took an interest in watercolor painting, and began painting illustrations of wildflowers that she saw on family trips to the Rocky Mountains of Canada. She also became interested in glaciers at that time.
See dozens of Mary Vaux Walcott's botanical illustrations, free from the Southwest School of Botanical Medicine.