Precise control of oligodendrocyte migration and development is critical for myelination of axons in the central nervous system (CNS), but important questions remain unanswered about the mechanisms controlling these processes. In a zebrafish screen for myelination mutants, we identified a mutation in zinc finger protein 16-like (znf16l). znf16l larvae have reduced myelin basic protein (mbp) expression and reduced CNS myelin. Marker, time-lapse, and ultrastructural studies indicated that oligodendrocyte specification, migration, and myelination are disrupted in znf16l mutants. Transgenic studies indicated that znf16l acts autonomously in oligodendrocytes. Expression of Zfp488 from mouse rescued mbp expression in znf16l mutants, indicating that these homologs have overlapping functions. Our results defined the function of a new zinc finger protein with specific function in oligodendrocyte specification, migration, and myelination in the developing CNS.