Plant litter breakdown is a key ecological process in terrestrial and freshwater ecosystems. Streams and rivers, in particular, have high rates of carbon dioxide evasion and they contribute substantially to global carbon fluxes. However, there is little information available on the relative roles of different drivers of plant litter breakdown in fresh waters, particularly at large scales. We present a global-scale study of litter breakdown in streams to compare the roles of biotic, climatic and other environmental factors on breakdown rates. We conducted an experiment in 24 streams encompassing latitudes from 47.8ºN to 42.8ºS, using litter mixtures of local species differing in quality and phylogenetic diversity, and alder (Alnus glutinosa) to control for variation in litter traits. Our models revealed that breakdown of alder was driven by climate, with some influence of pH, while variation in breakdown of litter mixtures was explained mainly by litter quality and phylogenetic diversity. The influence of these litter variables and pH was modulated by temperature, indicating that different mechanisms may operate at different latitudes. These results reflect global variability caused by multiple factors, but unexplained variance points to the need for expanded global-scale comparisons.