Austrian plant systematist from Vienna who was a student of and assistant to A.J. Kerner. He was appointed professor of botany at the University of Prague (1892) and later at the University of Vienna (1899). He was responsible for the Botanical Garden of the University of Vienna and redesigned the layout, also overseeing the construction of the Botanical Institute and Museum buildings. He was elected President of the Zoological-Botanical Society of Vienna (1901) and Vice-President of the Academy of Sciences (1919).

Wettstein was a pioneer of the integration of phylogeny with traditional taxonomy and published a great many new names and combinations, mostly concerning the Central European flora. He also published revisions of the genera Erysimum L. and Cheiranthus L. in the Brassicaceae, Hedreanthus (Hedraeanthus Griseb. = Edraianthus A. DC. nom. cons.) in the Campanulaceae, a monograph of the genus Euphrasia L., a revision of Apiaceae from Asia Minor published with O. Stapf, and accounts of the families Myoporaceae, Scrophulariaceae and Solanaceae for the multi-authored Die Nat⟼rlichen Pflanzenfamilien edited by A. Engler and K.A.E. Prantl.

From 1901 he worked on a guide to systematic botany (Handbuch der Systematischen Botanik) including a new classification of plants. The publication ran to several editions including the posthumous 5th edition (1935) edited by his son. Most of his plant collections were from Europe but he also collected in Brazil with V.F. Schiffner (1901). Plant specimens from Africa identified by the collector name 'Wettstein' are generally attributed to his son F. Wettstein, though both father and son participated in an expedition to Namibia, South Africa and Tanzania (1929-1930).