Plant architecture is a major target of rice (Oryza sativa) breeding and selection, but the underlying regulatory networks remain unclear. Here, we overexpressed an OsNAC2 mutant (OErN) that cannot be cleaved by the miRNA miR164b. OErN plants had better plant architecture and longer panicles, and produced more grains. The parental line averaged 12.2 primary and 31.5 secondary branches in the main panicles; two OErN lines averaged 15.0 and 15.2 primary, and 41.5 and 44.3 secondary branches. In large-scale field trials, OErN plants produced at least 58.62% more total grain (by weight) compared with the parental line. They also had more large and small vascular bundles in the stem internodes and leaves. Overexpression of miR164b or down-regulation of OsNAC2 led to decreased panicle length and grain yield in the main panicle. The OErN plants showed significant up-regulation of the grain number and plant architecture-related genes IPA1 and DEP1. A survey of >3000 rice varieties found no natural mutations in the miR164b-binding site of OsNAC2. OErN increased yield in Nipponbare and the commonly grown Yangyujing 3 cultivars. In summary, we identified an efficient new strategy to increase rice yield substantially and improve plant architecture through overexpression of OsmiR164b-resistant OsNAC2.