In 1816, he met Charles Alexandre Lesueur, a French naturalist, malacologist, and ichthyologist who soon became a member of the Academy and served as its curator until 1824.

To collect insects, he made numerous expeditions to frontier areas, risking American Indian attacks and hazards of traveling in wild countryside.

In 1819–20, Major Stephen Harriman Long led an exploration to the Rocky Mountains and the tributaries of the Missouri River, with Say as zoologist.

He traveled on the "Boatload of Knowledge" to the New Harmony Settlement in Indiana (1826–34), a utopian society experiment founded by Robert Owen.

She was an artist and illustrator of specimens, as in the book American Conchology, and was elected as the first woman member of the Academy of Natural Sciences.

[7] Other zoologists honored him by naming several taxa after him:[8] Frederick Valentine Melsheimer, also considered the "Father of Entomology"