Rheumatoid arthritis (RA) is a complex autoimmune disease with a substantial heritable component. We performed multi-ancestry genome-wide association meta-analyses of 351,498 individuals (comprising 39,600 RA cases and 311,898 controls) by integrating published and new datasets. This analysis identified 29 novel RA susceptibility loci and systematically classified association signals as population-specific, population-dominant, or population-shared between East Asian and European populations. Bayesian fine-mapping and functional annotation prioritized putative causal variants, highlighting 67 variants with posterior inclusion probability > 0.1 in novel loci, including an SLC27A6 missense variant (rs137898880) and a STIM1 3′ UTR variant (rs3750996). Our gene-prioritization framework combining genetic and biological evidence identified 203 high-confidence effector genes, 16 of which reside in novel loci (e.g., IFI16, AIM2, RGS1, ITPKB, CD80, RHOH, NFKB1, SIK3, and CCND2). Colocalization analysis leveraging tissue-specific eQTL datasets provided mechanistic insights by implicating shared causal variants underlying RA association signals. Notably, the transcription factor gene RUNX3 at a novel locus showed evidence of cis-regulation in immune cells, and RUNX3-binding sites were enriched for variants explaining excess RA heritability, supporting a role for RUNX3 as a trans-regulatory mediator of RA risk at distal RA loci. Finally, gene-drug interaction networks weighted by RA association strength highlighted population-informed therapeutic opportunities and drug-repurposing targets driven largely by novel loci.