Seed size is an important yield and quality-determining trait in higher plants and is also crucial to their evolutionary fitness. In African yam bean (AYB), seed size varies widely among different accessions. However, the genetic basis of such variation has not been adequately documented. A genome-wide marker-trait association study was conducted to identify genomic regions associated with four seed size traits (seed length, seed width, seed thickness, and 100-seed weight) in a panel of 195 AYB accessions. A total of 5416 SNP markers were generated from the diversity array technology sequence (DArTseq) genotype-by-sequencing (GBS)- approach, in which 2491 SNPs were retained after SNP quality control and used for marker-trait association analysis. Significant phenotypic variation was observed for the traits. Broad-sense heritability ranged from 50.0% (seed width) to 66.4% (seed length). The relationships among the traits were positive and significant. Genome-wide association study (GWAS) using the general linear model (GLM) and the mixed linear model (MLM) approaches identified 12 SNP markers significantly associated with seed size traits across the six test environments. The 12 makers explained 6.5–10.8% of the phenotypic variation. Two markers (29420334|F|0-52:C>G-52:C>G and 29420736|F|0-57:G>T-57:G>T) with pleiotropic effects associated with seed width and seed thickness were found. A candidate gene search identified five significant markers (100026424|F|0-37:C>T-37:C>T, 100041049|F|0-42:G>C-42:G>C, 100034480|F|0-31:C>A-31:C>A, 29420365|F|0-55:C>G-55:C>G, and 29420736|F|0-57:G>T-57:G>T) located close to 43 putative genes whose encoding protein products are known to regulate seed size traits. This study revealed significant makers not previously reported for seed size in AYB and could provide useful information for genomic-assisted breeding in AYB.