Background: Antibiotic resistance (ABR) is a major concern for global health. However, factors driving its emergence and dissemination are not fully understood. Identification of such factors is crucial to explain heterogeneity in ABR rates observed across space, time, and species and antibiotics. Methods: We analysed count data of clinical isolates from 51 countries over 2006–19 for thirteen drug-bacterium pairs taken from the ATLAS database. We characterised ABR spatial and temporal patterns and used a mixed-effect negative binomial model, accounting for country-year dependences with random effects, to investigate associations with potential drivers, including antibiotic sales, economic and health indicators, meteorological data, population density, and tourism. Findings: ABR patterns were strongly country and drug–bacterium pair dependent. In 2019, median ABR rates ranged from 6·3% (IQR 19·7% [0·5–20·2]) for carbapenem-resistant Klebsiella pneumoniae to 80·7% (41·8% [50·4–92·2]) for fluoroquinolone-resistant Acinetobacter baumannii, with heterogeneity across countries. From 2006 to 2019, carbapenem resistance increased in more than 60% of investigated countries; no global trend was observed for other resistances. Multivariable analyses identified significant associations of ABR with country-level selecting antibiotic sales, but only in fluoroquinolone-resistant-Escherichia coli, fluoroquinolone-resistant-Pseudomonas aeruginosa, and carbapenem-resistant-A baumannii. We also found a correlation between temperature and resistance in Enterobacteriaceae and with the health system quality for all drug–bacterium pairs except Enterococci and Streptococcus pneumoniae pairs. Despite wide consideration of possible explanatory variables, drug–bacterium pair ABR rates still showed unexplained spatial random effects variance. Interpretation: Our findings reflect the diversity of mechanisms driving global antibiotic resistance across pathogens and stress the need for tailored interventions to tackle bacterial resistance. Funding: Independent research Pfizer Global Medical Grant and ANR Labex IBEID.