Differential local adaptation restricts gene flow between populations inhabiting distinct environments, resulting in isolation by adaptation. In addition to the statistical inferences of genotype–environment associations, an integrative approach is needed to investigate the effect of local adaptation on population divergence at the ecological, genetic and genomic scale. Here, we combine reciprocal transplant, genome–environment association and QTL mapping to investigate local adaptation inBoechera stricta(Drummond's rockcress). With reciprocal transplant experiment, we found local genetic groups exhibit phenotypic characteristics corresponding to the distinct selection forces from different water availability. At the genetic level, the local allele of a major fitness QTL confers higher and sturdier flowering stalks, maximizing the fecundity fitness component under sufficient water supply, and its genetic variation is associated with precipitation across the landscape. At the genomewide scale, we further showed that multiple loci associated with precipitation are highly differentiated between genetic groups, suggesting that local adaptation has a widespread effect on reducing gene flow. This study provides one of the few comprehensive examples demonstrating how local adaptation facilitates population divergence at the trait, gene and genome level.