Grain number per panicle (GNP) is a major determinant of grain yield in cereals. However, the mechanisms that regulate GNP remain unclear. To address this issue, we isolate a series of sorghum [Sorghum bicolor (L.) Moench] multiseeded (msd) mutants that can double GNP by increasing panicle size and altering floral development so that all spikelets are fertile and set grain. Through bulk segregant analysis by next-generation sequencing, we identify MSD1 as a TCP (Teosinte branched/Cycloidea/PCF) transcription factor. Whole-genome expression profiling reveals that jasmonic acid (JA) biosynthetic enzymes are transiently activated in pedicellate spikelets. Young msd1 panicles have 50% less JA than wild-type (WT) panicles, and application of exogenous JA can rescue the msd1 phenotype. Our results reveal a new mechanism for increasing GNP, with the potential to boost grain yield, and provide insight into the regulation of plant inflorescence architecture and development.