Professor Keene began teaching at Columbia University in 1955, and was named Columbia University Shincho Professor of Japanese Literature in 1986 and University Professor in 1989; he was University Professor Emeritus and Shincho Professor Emeritus. Professor Keene had published approximately 25 books in English, consisting of studies of Japanese literature and culture, translations of Japanese works of both classical and modern literature, a four-volume history of Japanese literature, and edited works including two anthologies of Japanese literature and the collection Twenty Plays of the No Theatre. Professor Keene's Japanese publications included approximately 30 books, some written originally in Japanese, others translated from English.

In 2002, Professor Keene's Meiji Tenno (Shinchosha, 2001; translation by Yukio Kakuchi), a biography of the Meiji Emperor, won the 56th Mainichi Shuppan Culture Prize in the Humanities and Social Sciences division. The English text, Emperor of Japan: Meiji and His World, 1852–1912, was published by Columbia University Press in the same year, and, among many enthusiastic reviews, was named one of the Best Books of 2002 by the Los Angeles Times Book Review.