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Moderate heat stress accompanied by short episodes of extreme heat during the post-anthesis stage is common in most US wheat growing areas and causes substantial yield losses. Sink strength (grain number) is a key yield limiting factor in modern wheat varieties. Increasing spike fertility (SF) and improving the partitioning of assimilates can optimize sink strength which is essential to improve wheat yield potential under a hot and humid environment. A genome-wide association study (GWAS) allows identification of novel quantitative trait loci (QTLs) associated with SF and other partitioning traits that can assist in marker assisted breeding. In this study, GWAS was performed on a soft wheat association mapping panel (SWAMP) comprised of 236 elite lines using 27,466 single nucleotide polymorphisms (SNPs). The panel was phenotyped in two heat stress locations over 3 years. GWAS identified 109 significant marker-trait associations (MTAs) (p ≤ 9.99 x 10−5) related to eight phenotypic traits including SF (a major component of grain number) and spike harvest index (SHI, a major component of grain weight). MTAs detected on chromosomes 1B, 3A, 3B, and 5A were associated with multiple traits and are potentially important targets for selection. More than half of the significant MTAs (60 out of 109) were found in genes encoding different types of proteins related to metabolism, disease, and abiotic stress including heat stress. These MTAs could be potential targets for further validation study and may be used in marker-assisted breeding for improving wheat grain yield under post-anthesis heat stress conditions. This is the first study to identify novel QTLs associated with SF and SHI which represent the major components of grain number and grain weight, respectively, in wheat.