Early leaf senescence in wheat (Triticum aestivum L.) is one of the limiting factors for developing high yield potential. In this study, a stably inherited, early leaf-senescence mutant LF2099 was initially identified in an M₂ population of the common wheat accession H261 after ethyl methanesulfonate (EMS) mutagenesis. Early leaf senescence was observed in the LF2099 mutant during the three-leaf-stage, and then the etiolated area of the wheat leaf increased gradually from the bottom to the top throughout development. Compared with H261, the chlorophyll (Chl a, Chl b) and carotenoid contents and photosynthetic capacity of the mutant were significantly decreased. All of its yield-related traits except for spike length were also significantly reduced. Dissolved cytoplasm, abnormal chloroplast structure, dissolved chloroplast membrane, abnormal thylakoid development, and more plastoglobules were observed in the senescent leaf region of the mutant by transmission electronic microscope. Genetic analysis indicated that the early leaf-senescence phenotype is controlled by an incomplete-dominance nuclear gene, here designated Els2. Using single nucleotide polymorphisms and bulked segregant analysis, the els2 gene was anchored in a region on chromosome 2BL between simple sequence repeat (SSR) markers gpw4043 and wmc149. Six new polymorphic SSR markers were developed from the Chinese Spring 2BL shotgun survey sequence contigs. By means of comparative genomics analyses, the collinearity genomic regions of the els2 locus on wheat 2BL were identified in Brachypodium distachyon chromosome 5, rice (Oryza sativa) chromosome 4 and sorghum (Sorghum bicolor) chromosome 6. Five intron polymorphism (IP) markers were further developed from this collinearity genomic region. Ultimately, Els2 was mapped in a genetic interval of 0.95 cM flanked by IP markers 2BIP09 and 2BIP14. The co-segregating IP markers 2BIP12 and 2BIP17 provide a starting point for the fine mapping and map-based cloning of Els2.