In June 1877 Morse first visited Japan in search of coastal brachiopods. His visit turned into a three year stay when he was offered a post as the first Professor of Zoology at the Tokyo Imperial University. He went on to recommend several fellow Americans as o-yatoi gaikokujin (foreign advisors) to support the modernization of Japan in the Meiji Era. In order to collect specimens, he established a marine biological laboratory at Enoshima in Kanagawa Prefecture. While looking out of a window on a train between Yokohama and Tokyo, Morse discovered the Ōmori shell mound, the excavation of which opened the study in archaeology and anthropology in Japan, and shed much light on the material culture of prehistoric Japan. He returned to Japan in 1881 to present a report of his findings to Tokyo Imperial University.

While in Japan, he authored a book Japanese Homes and Their Surroundings illustrated with his own line drawings. He also made a collection of over 5,000 pieces of Japanese pottery.

Morse also had much interest in Japanese ceramics,[2] he returned on a third visit to Japan in 1882, during which he collected clay samples as well as finished ceramics. He also brought back to Boston a collection amassed by government minister and not art collector Ōkuma Shigenobu, who donated it to Morse in recognition of his services to Japan. These now form part of the "Morse Collection" of Museum of Fine Arts in Boston, whose catalog was written by Ernest Francisco Fenollosa. His collection of daily artifacts of the Japanese people is kept at the Peabody Essex Museum in Salem, Massachusetts.