Sugarcane (Saccharum spp.) is an important economic crop, contributing up to 80% of sugar and approximately 60% of biofuel globally. To meet the increased demand for sugar and biofuel supplies, it is critical to breed sugarcane cultivars with robust performance in yield traits. Therefore, dissection of causal DNA sequence variants is of great importance, as it provides genetic resources and fundamental information for crop improvement. In this study, we analyzed nine yield traits in a sugarcane diversity panel consisting of 308 accessions primarily selected from the World Collection of Sugarcane and Related Grasses. By genotyping the diversity panel via target enrichment sequencing, we identified a large number of sequence variants. Genome-wide association studies between the markers and traits were conducted, taking dosages and gene actions into consideration. In total, 217 nonredundant markers and 225 candidate genes were identified to be significantly associated with the yield traits, which can serve as a comprehensive genetic resource database for future gene identification, characterization, and selection for sugarcane improvement. We further investigated runs of homozygosity (ROH) in the sugarcane diversity panel. We characterized 282 ROHs and found that the occurrence of ROHs in the genome were nonrandom and probably under selection. The ROHs were associated with total weight and dry weight, and high ROHs resulted in a decrease in the two traits. This study suggests that genomic inbreeding has led to negative impacts on sugarcane yield. Abbreviations: DAPC, discriminant analysis of principal components; GWAS, genome-wide association study; indels, insertions and deletions; NGS, next-generation sequencing; NROH, total number of ROHs; ROH, run of homozygosity; SROH, sum total length of ROHs; SNP, single nucleotide polymorphisms; TES, target enrichment sequencing; WCSRG, world collection of sugarcane and related grasses. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.