As an entomologist he discovered more than 20 new species of North American butterflies and introduced the Florissant Fossil Beds in Colorado to the wider scientific world.

As a horticulturist, he is best known for his pioneering work on the growing and crossbreeding of orchids, and the creation of new forms of caladium, bromeliad, crinum, amaryllis and hemerocallis (daylily).

Schooled in America and in Europe, where he learned French and German and studied the classics, he developed a deep interest in natural sciences from an early age that was strongly encouraged by his parents.

[11] At the end of his collecting time in Colorado, in September 1871, he heard tell of a strange petrified forest and rock formation at Florissant and went there on horseback to investigate.

In this year he sold his extensive butterfly collection to the Carnegie Museum of Natural History in Pittsburgh and turned his attention to horticulture.

[14] He counted fellow student and fraternity brother Louis Agassiz Fuertes, the famous bird artist, among his closest friends.

[15] Still uncertain as to his future vocation, in 1878 Mead and his parents embarked on a six-month long entomological and nature trip to California and the Western States, travelling by steamer from New York via Panama and up the coast to San Francisco, returning via Salt Lake City and Chicago.

In 1886, he purchased eighty-five acres in Oviedo, Florida, close to Lake Charm where orange grove land was more fertile, choosing a location next to Edith's aunt Mary.

She had previously married Dr. Henry Foster owner of the Clifton Springs Sanitarium in New York State, and the couple were winter visitors to the Lake Charm area.

At Lake Charm Mead grew many palms from seed and hybridized orchids, bromeliads, crinum and later, caladium, amaryllis and daylilies.

Many growers abandoned their groves entirely, but Mead recognized that below ground artesian water at a constant 70 degrees might provide relief from frost and allow citrus trees to survive freezing temperatures.

He successfully covered an acre of oranges, installed a pump and irrigation system, and proved the concept, the first known description[16] of a technique still used today.

By then Mead had realized that germination rates could be made more favorable in a sterile and temperature-controlled environment[20] akin to clean room conditions in a laboratory.

[21] It has been stated[22] as being doubtful whether Knudson would have been successful without Mead's inputs and donation of viable ripe orchid seeds, so arguably he should have been credited as a co-discoverer.