Genome-wide association studies were conducted using a globally diverse safflower (Carthamus tinctoriusL.) Genebank collection for grain yield (YP), days to flowering (DF), plant height (PH), 500 seed weight (SW), seed oil content (OL), and crude protein content (PR) in four environments (sites) that differed in water availability. Phenotypic variation was observed for all traits. YP exhibited low overall genetic correlations (rGoverall) across sites, while SW and OL had highrGoveralland high pairwise genetic correlations (rGij) across all pairwise sites. In total, 92 marker-trait associations (MTAs) were identified using three methods, single locus genome-wide association studies (GWAS) using a mixed linear model (MLM), the Bayesian multi-locus method (BayesR), and meta-GWAS. MTAs with large effects across all sites were detected for OL, SW, and PR, and MTAs specific for the different water stress sites were identified for all traits. Five MTAs were associated with multiple traits; 4 of 5 MTAs were variously associated with the three traits of SW, OL, and PR. This study provided insights into the phenotypic variability and genetic architecture of important safflower agronomic traits under different environments.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11032-022-01295-8.