While substantial research supports the role of parent–child interactions on the emergence of psychiatric symptoms, few studies have explored biological mechanisms for this association. The current study explored behavioral and neural parent–child synchronization during frustration and play as predictors of internalizing and externalizing behaviors across a span of 1.5 years. Parent–child dyads first came to the laboratory when the child was 4–5 years old and completed the Disruptive Behavior Diagnostic Observation Schedule: Biological Synchrony (DB-DOS: BioSync) task while functional near-infrared spectroscopy (fNIRS) data were recorded. Parents reported on their child's internalizing and externalizing behaviors using the Child Behavior Checklist (CBCL) four times over 1.5 years. Latent growth curve (LGC) modeling was conducted to assess neural and behavioral synchrony as predictors of internalizing and externalizing trajectories. Consistent with previous investigations in this age range, on average, internalizing and externalizing behaviors decreased over the four time points. Parent–child neural synchrony during a period of play predicted rate of change in internalizing but not externalizing behaviors such that higher parent–child neural synchrony was associated with a more rapid decrease in internalizing behaviors. Our results suggest that a parent–child dyad's ability to coordinate neural activation during positive interactions might serve as a protective mechanism in the context of internalizing behaviors.