Reduction in vegetative branching is commonplace when crops are domesticated from their wild progenitors. We have identified genetic loci responsible for these changes in foxtail millet (Setaria italica), a crop closely related to maize but whose genetics are little known. Quantitative trait locus (QTL) analysis and comparative genomics reveal that basal branching (tillering) and axillary branching are partially controlled by separate loci, and that the orthologue of teosinte branched1, the major gene controlling branching phenotype in maize, has only a minor and variable effect. We identify other candidate genes for control of branching, including a number of hormone biosynthesis pathway genes. These results suggest that similar phenotypic effects may not be produced by orthologous loci, even in closely related species, and that results from well characterized model systems such as maize must be reviewed critically before being applied to other species.