He did his doctoral studies in Linguistics at the University of California, Berkeley, where Mary Haas, co-founder of the department, was then chair. Haas had been a student of Edward Sapir while at University of Chicago and Yale University, and through her own extensive research in descriptive and documentary linguistics had become a specialist in Native American languages and an authority on Thai. Haas was instrumental in Matisoff’s decision to research a language of mainland Southeast Asia for his dissertation. Matisoff's doctoral dissertation was a grammar of the Lahu language, a Tibeto-Burman language belonging to the Loloish branch of the family. He spent a year in northern Thailand doing field work on Lahu during his graduate studies with support from a Fulbright-Hays Fellowship. He completed his PhD in Linguistics in 1967, and made several field studies thereafter through an American Council of Learned Societies fellowship. His Grammar of Lahu is notable both for its depth of detail and the theoretical eclecticism which informed his description of the language. He later published an extensive dictionary of Lahu and a corresponding . After four years teaching at Columbia University, Matisoff accepted a professorship at Berkeley. At Berkeley, his research has encompassed a wide range of topics, from historical and comparative linguistics to tonal phenomena, variational semantics, language contact, Yiddish, and Tibeto-Burman morphosyntax. Before his retirement, he taught classes on the Linguistics of Southeast Asia, Tibeto-Burman Linguistics, Historical Semantics, Morphology, and Field Methods. In Field Methods, graduate students learn the methods of language description through eliciting data from a native speaker. The languages studied in Matisoff’s field methods classes in different years include: Lai Chin, Sherpa, and Uighur, among numerous others. Matisoff has coined a number of terms used in linguistics, including tonogenesis, rhinoglottophilia, Sinosphere and Indosphere, Cheshirisation, which refers to the trace remains of an otherwise disappeared sound ina word, and sesquisyllabic to describe the iambic stress pattern of words in languages spoken in Southeast Asia, such as the Mon–Khmer languages. He edited the journal ' for many years. Matisoff participated in establishing the ', an annual conference since 1968. In 1987, Matisoff began the project, an historical linguistics project aimed at producing an etymological dictionary of Sino-Tibetan organized by semantic field. The project maintains a of nearly one million records with data on Sino-Tibetan languages from over 500 sources. This database is used to identify and mark cognates for the purposes of better understanding the historical development of the Sino-Tibetan language family and the subgroupings of the languages therein, and to reconstruct the theoretical proto-language of the language family, Proto-Sino-Tibetan. Matisoff has authored two monographs so far presenting results from the STEDT project: ' and '. Although Matisoff retired from Berkeley in 2002, he continues to publish extensively and is Principal Investigator for the STEDT project until its end in 2015. In 2015, the final print and software releases for STEDT were disseminated to the public, concluding the decades-long Sino-Tibetan Etymological Dictionary and Thesaurus.
