In 1958 Rothenberg founded Hawk's Well Press, which published early works by Robert Kelly, Diane Wakoski, Armand Schwerner, and Rochelle Owens, as well as Rothenberg's first book of poems, White Sun Black Sun. As an adjunct to these activities, Rothenberg edited the magazine Poems from the Floating World.

Rothenberg's concern for the relationship between "primitive" and modern poetry led to the development of an anthology of primitive and archaic poetry, Technicians of the Sacred (1968). This work attempted to redefine the range of primitive poetry, presenting not only words of songs, but picture poems, sound poetry, naming poems, dreams and visions and scenarios of ritual-events. With the completion of this work, Rothenberg directed his attention to ethnopoetics and began a study of Senecan Indian songs at the the Allegheny Reservation in Steamburg, New York.

In 1968 Rothenberg received a grant from the Wenner-Gren Foundation in Anthropological Research to conduct a two-part experiment in the translation of American Indian poetry. The project involved a collaborative translation between Rothenberg and Seneca songmen and the translation of a series of Navajo horse-blessing songs. In this effort, Rothenberg began to develop an approach he termed "total translation," meaning that he accounted in the English version for every element in the original language, including the so-called "meaningless" vocables, word distortions and redundancies. This close study and involvement with American Indian poetry and ritual promoted the development of Rothenberg's next anthology, Shaking the Pumpkin: Traditional Poetry of the Indian North Americas (1972).

Since 1960, Rothenberg has served as an instructor at various colleges and universities, including: the City College of New York (1960-1961); the Mannes College of Music, New York City (1961-1970); the University of California, San Diego (Regents' Professor, 1971); the New School for Social Research (1971-1972); the University of Wisconsin, Milwaukee (1974-1976); San Diego State University (1976-1977); the University of California, San Diego (1977-1985); SUNY Albany (Writer in Residence, 1986); SUNY Binghampton (1986-1988); and the University of California, San Diego (1988- ).

Finally, Rothenberg has translated work by Paul Celan, Hans Magnus Enzensberger, Eugen Gomringer, Rolf Hochhuth, Garcia Lorca, Kurt Schwitters and many other European writers into English.