Leaf rust of wheat (Triticum aestivum L.) is a major disease that causes significant yield losses worldwide. The short-lived nature of leaf rust resistance (Lr) genes necessitates a continuous search for novel sources of resistance. We performed a genome-wide association study (GWAS) on a panel of 1596 wheat accessions. The panel was evaluated for leaf rust reaction by testing with a bulk of Puccinia triticina Eriks. (Pt) isolates collected from multiple fields of Oklahoma in 2013 and two predominant races in the fields of Oklahoma in 2015. The panel was genotyped with a set of 5011 single-nucleotide polymorphism (SNP) markers. A total of 14 quantitative trait loci (QTL) for leaf rust resistance were identified at a false discovery rate (FDR) of 0.01 using the mixed linear model (MLM). Of these, eight QTL reside in the vicinity of known genes or QTL, and more studies are needed to determine their relationship with known loci. QLr.stars-7AL1 is a new QTL to bread wheat but is close to a locus previously identified in durum wheat [Triticum turgidum L. subsp. durum (Desf.) Husn.]. The other five QTL, including QLr.stars-1BL3, QLr. stars-1DC1, QLr.stars-2BL1, QLr.stars-5BL1, and QLr.stars-7AS1, are likely novel loci for leaf rust resistance. The uneven distribution of the 14 QTL in the six subpopulations of the panel suggests that wheat breeders can enhance leaf rust resistance by selectively introgressing some of these QTL into their breeding materials. In addition, another 31 QTL were significantly associated with leaf rust resistance at a FDR of 0.05.