An expert in the field of ornithology, Lewis is remembered as a pioneer female American scientist as well as an activist in the anti-slavery, temperance, and women's suffrage movements.

[4] She also serving as a role model in social activism by housing fugitive slaves as part of the Underground Railroad to freedom in Canada.

[3] Following the completion of her studies in 1842, she entered the teaching profession, which was one of the few career fields open to educated women in the day, taking a position as a teacher of botany and chemistry at a boarding school in York, Pennsylvania, run by her uncle Bartholomew Fussell.

[6] She met one of America's leading ornithologists, John Cassin of the Philadelphia Academy of Natural Sciences, in 1862 and studied ornithology at an advanced level under his tutorship for the next half decade.

[9] As a product of a devout religious upbringing, Lewis was critical of the Charles Darwin's theory of evolution for much of her life, instead positing that God was responsible for an intricate and well ordered universe.

[9] Held back by her theistic determinism and lack of higher education, Lewis was forced to limit herself to popular lectures on the naturalism to work as a freelance scientific illustrator, by which she made her living.

[2] She applied for a number of academic posts throughout the period, including a vacant professorship of natural history at Vassar, but owing to her lack of formal education beyond the high school level and a pervasive sexism in academia she was unable to land a college-level teaching position.

[11] In addition to her direct action against slavery as part of the secret network which aided escaped African-American slaves in their flight to freedom in the years prior to the American Civil War, Lewis was active in several other social movements of her day.

[14] Included in this archival holding are Lewis's papers and drawings relating to the natural sciences, as well as an unpublished manuscript of a memoir of the Underground Railroad.

[14] In 2014, a Commonwealth of Pennsylvania roadside historical marker honoring Lewis was erected in East Pikeland Township at 2123 Kimberton Road, Phoenixville, near the site of her family's farm.