Peste des petits ruminants (PPR) is an acute, severe, and highly contagious disease caused by peste des petits ruminants virus (PPRV), which primarily induces tissue damage through the formation of syncytia. Therefore, elucidating the molecular mechanism underlying PPRV-induced syncytium formation is of critical importance. In this study, we generated Vero CCL-81 cell lines stably expressing the PPRV receptors SLAM (lymphocytic) or Nectin-4 (epithelial) and further found that PPRV infection significantly induced syncytium formation in these cell lines as well as in goat mammary epithelial cells (GMECs) and ovine rumen epithelial cells (ORECs). Furthermore, the viral H and F proteins served as the pivotal determinants of syncytium formation. More importantly, we discovered that PPRV-induced syncytium formation is dependent on the RhoA-Rock1 signaling pathway and that inhibition of syncytium formation markedly suppressed PPRV replication. Collectively, our findings provide novel insights into the molecular mechanism of PPRV-induced syncytium formation, offer theoretical references for the development of new antiviral strategies, and advance the scientific eradication of PPR.