Nitrogen fixation efficiency is a desired trait in agriculture. Here we study nitrogen fixation traits in chickpea (Cicer arietium), which has special relevance given the crop’s predominance as an important source of protein and nutrition in the developing world. This study seeks to understand the relevance of genetic and transcriptional diversity of both the crop (C. arietinum), its two wild relatives C. reticulatum and C. echinospermum, and their cognate symbiotic microbes Mesorhizobium mediterraneum and M. ciceri. The experiments test the hypothesis that local adaptation is an ecological mechanism operating in wild systems to optimize biological nitrogen fixation, by quantifying biomass gain and nodulation phenotypes in a network of naturally-occurring host and bacterial genotype combinations. Plant biomass gain was greater for native (homologous) compared to non-native (heterologous) plant-bacteria combinations, leading to the conclusion that nitrogen fixation per se is more effective in co-evolved plant-microbe pairs, providing strong evidence of local adaptation in natural systems. C. echinospermun has effective symbiosis with its native, homologous symbiont M. ciceri and it is incompatible (nod-) with the heterologous symbiont M. mediterraneum. Conversely, C. reticulatum has more effective symbiosis with its native, homologous symbiont M. mediterraneum compared to heterologous M. ciceri. Interestingly, C. reticulatum has similar nodulation phenotypes with both bacterial species, and thus increased biomass gain in the homologous interaction is interpreted as greater efficiency of nitrogen fixation. The analysis of recombinant inbred lines derived from C. echinospermum X C. arietinum inoculated with either M. mediterraneum or M. ciceri document genetic segregation of symbiotic specificity, providing the basis for molecular genetic studies. Transcriptional profiling analysis of compatible and incompatible symbiotic pairs revealed responses to nitrogen (symbiotic and inorganic) that are both common and different among plant species. In particular, enhanced transcription of genes related to carbon metabolism and plastid-related functions is characteristic of M. ciceri nodules, while interaction with M. mediterraneum is associated with upregulation a diversity of processes, including nitrogen related gene expression, but largely exclusive of carbon metabolism. Whole genome analyses were used to characterize bacterial strains associated with chickpea cultivation in Pakistan and strains from the wild’s center of origin in South-Eastern Turkey. The analysis focused, in particular, on the provenance of genes involved in Type III secretion and Nod factor synthesis, informing us about the evolution of bacterial symbiosis in chickpea and bacterial loci relevant in the host-microbe interaction. The understanding gained from these studies informs fundamental questions about Cicer-Mesorhizobium co-evolution, and also has two broad practical implications: (1) for breeding of modern cultivars with improved biological nitrogen fixation, and (2) for developing improved microbial inoculants.