Association mapping is a method to identify associations between target traits and genetic markers based on linkage disequilibrium (LD) of a quantitative trait locus. Synthetic hexaploid wheat (SHW) is derived from a cross between Triticum durum Desf. and Aegilops tauschii Coss. that enhances genetic diversity and broadens breeding resources. In this study, phenotypic diversity in 110 wheat accessions (86 SHW germplasm specimens and 24 conventional wheat varieties) was evaluated quantitatively for yield characteristics of grains per spike, thousand kernel weight, and spike length. Phenotypic data were collected over two years at two locations, and 1785 alleles were detected (mean 6.59), ranging from 3 to 11 alleles per locus. The average genetic diversity index was 0.749, with a range from 0.239 to 0.923. The polymorphic information content (PIC) ranged from 0.145 to 0.968, with a mean value of 0.695. The genetic diversity index and PIC indicated that genome B > D > A. Accessions were grouped into three subgroups based on STRUCTURE and unweighted pair-group with arithmetic mean clustering. The mean LD decay across the genome was 11.78 cM. Association mapping between traits and simple sequence repeat markers was performed using the generalized linear model approach. Forty-six SSR loci were significantly associated with the measured agronomic traits in two geographic locations. Together, these results broaden our knowledge of how to harness elite genes and genetic diversity in SHW in genomic and marker-assisted selection.