Recently, emerging evidence has shown that Stat3 controls tumor cell migration and invasion. However, the molecular mechanisms by which Stat3 controls the cell movement remain largely unknown. Embryonic gastrula progenitors display coordinated and orientated migration, called collective cell migration. Collective cell migration is the simultaneous movement of multiple cells and is universally involved in physiological and pathological programs. Stat3 activity is required for the migration of gastrula progenitors, but it does not affect cell specification, thus suggesting that gastrula movements are an excellent model to provide insight into Stat3 control of cell migration in vivo. In this study, we reveal a novel mechanism by which Stat3 modulates extracellular matrix (ECM) assembly to control the coherence of collective migration of prechordal plate progenitors during zebrafish embryonic gastrulation. We show that Stat3 regulates the expression of Efemp2a in the prechordal plate progenitors that migrate anteriorly during gastrulation. Alteration of Stat3-Efemp2a signaling activity disrupted the configuration of fibronectin (FN) and laminin (LM) matrices, resulting in defective coherence of prechordal plate progenitor movements in zebrafish embryos. We demonstrate that Efemp2a acts as a downstream effector of Stat3 to promote ECM configuration for coherent collective cell migrations in vivo.