Signal transducers and transcription factors are used in common for developmental cell migration, vasculogenesis, branching morphogenesis, as well as neuronal pathfinding. STAT3, a transcription factor, has been shown to function in all of these processes except neuronal pathfinding. Here, it is shown that STAT3 also facilitates this process. Elimination of STAT3 signaling results in half of zebrafish CaP motoneurons stalling along their ventral pathfinding trajectory. Conversely, constitutive activation leads to precocious branching and redefines CaP axons as a responding population to dorsal guidance cues, resulting in bifurcated axons innervating normal ventral targets as well as additional dorsal muscle groups. These results are consistent with and highlight a fundamental role for STAT3 as a factor promoting cellular responses to guidance cues, not only in nonneural cells but also in pathfinding neurons.