Antimicrobial resistance (AMR) is a major threat to global health. Understanding the
emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs)
is essential to develop sustainable strategies combatting this threat. Here, we use
metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101
countries, collected from 2016 to 2019. We find regional patterns in resistomes, and
these differ between subsets corresponding to drug classes and are partly driven by
taxonomic variation. The genetic environments of 49 common ARGs are highly diverse,
with most common ARGs carried by multiple distinct genomic contexts globally and sometimes
on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal
limitation and global transmission. Our data furthermore suggest certain geographies
are more prone to transmission events and should receive additional attention.