Seed-cotton yield (SY) and lint yield (LY) are the most important yield traits of cotton. Thus, it is critical to dissect their genetic architecture. Upland cotton (Gossypium hirsutum) is widely grown worldwide. In this study, a genome-wide association mapping was performed based on the CottonSNP80K array to dissect the genetic architecture of SY and LY in Upland cotton. Twenty-three significant associations were detected within four environments, including 11 associated with SY and 12 associated with LY. Seven single nucleotide polymorphisms (SNPs), TM234, TM237, TM247, TM255, TM256, TM263, and TM264, were co-associated with the two traits, which may indicate pleiotropy or intergenic tight linkages. Five SNPs, TM13332, TM39771, TM57119, TM81653, and TM81660, were coincided with those of previous reports and could be used in marker-assisted selection. Combining functional annotations with expression analyses of the genes identified within 400 kb of the significantly associated SNPs, we hypothesize that the three genes, Gh_D05G1077 and Gh_D13G1571 for SY, and Gh_A11G0775 for LY, may have the potential to increase cotton yield. The results would provide useful information for understanding the genetic basis of yield traits in Upland cotton and for facilitating its high-yield breeding through molecular design.