In wheat, a multi-locus genome-wide association study (ML-GWAS) was conducted for the four grain weight-related traits (days to anthesis, grain filling duration, grain number per ear, and grain weight per ear) using data recorded under irrigated (IR) and rain-fed (RF) conditions. Seven stress-related indices were estimated for these four traits: (i) drought resistance index (DI), (ii) geometric mean productivity (GMP), (iii) mean productivity index (MPI), (iv) relative drought index (RDI), (v) stress tolerance index (STI), (vi) yield index, and (vii) yield stability index (YSI). The association panel consisted of a core collection of 320 spring wheat accessions representing 28 countries. The panel was genotyped using 9,627 single nucleotide polymorphisms (SNPs). The genome-wide association (GWA) analysis provided 30 significant marker-trait associations (MTAs), distributed as follows: (i) IR (15 MTAs), (ii) RF (14 MTAs), and (iii) IR+RF (1 MTA). In addition, 153 MTAs were available for the seven stress-related indices. Five MTAs co-localized with previously reported QTLs/MTAs. Candidate genes (CGs) associated with different MTAs were also worked out. Gene ontology (GO) analysis and expression analysis together allowed the selection of the two CGs, which may be involved in response to drought stress. These two CGs included: TraesCS1A02G331000 encoding RNA helicase and TraesCS4B02G051200 encoding microtubule-associated protein 65. The results supplemented the current knowledge on genetics for drought tolerance in wheat. The results may also be used for future wheat breeding programs to develop drought-tolerant wheat cultivars.