His most important contribution to his field was the development of a new classification system for African Languages, which he finally published in 1963. While the languages of Eurasia and the Pacific Ocean islands have proven largely susceptible to classification, a major embarrassment to historical linguistics was the inability to do the same for the Americas, Australia, and Africa. Greenberg's cracking of the latter is rightly considered a major step forward (after some initial criticism).
He later worked on the classification of South American languages and of the languages of New Guinea, and more recently made a controversial attempt to marry several major language families in the manner of the old Nostratic language hypothesis. He also conducted research on universally used grammar principles (s. Greenberg Universals).