Antibiotic resistance poses a significant threat to human health, and wastewater treatment plants (WWTPs) are important reservoirs of antibiotic resistance genes (ARGs). Here, we analyze the antibiotic resistomes of 226 activated sludge samples from 142 WWTPs across six continents, using a consistent pipeline for sample collection, DNA sequencing and analysis. We find that ARGs are diverse and similarly abundant, with a core set of 20 ARGs present in all WWTPs. ARG composition differs across continents and is distinct from that of the human gut and the oceans. ARG composition strongly correlates with bacterial taxonomic composition, with Chloroflexi, Acidobacteria and Deltaproteobacteria being the major carriers. ARG abundance positively correlates with the presence of mobile genetic elements, and 57% of the 1112 recovered high-quality genomes possess putatively mobile ARGs. Resistome variations appear to be driven by a complex combination of stochastic processes and deterministic abiotic factors.