Mutations in the highly conserved Pax6 transcription factor have been implicated in neurodevelopmental disorders and behavioral abnormalities, yet the mechanistic basis of the latter remain poorly understood. Our study, using behavioral phenotyping, has identified aberrant social interactions, characterized by withdrawal behavior, and olfactory deficits in Pax6 heterozygous mutant mice. The molecular mechanisms underlying the observed phenotypes were characterized by means of RNA-sequencing on isolated olfactory bulbs followed by validation with qRT-PCR. Comparative analysis of olfactory bulb transcriptomes further reveals an imbalance between neuronal excitation and inhibition, synaptic dysfunction, and alterations in epigenetic regulation as possible mechanisms underlying the abnormal social behavior. We observe a considerable overlap with autism-associated genes and suggest that studying Pax6-dependent gene regulatory networks may further our insight into molecular mechanisms implicated in autistic-like behaviors in Pax6 mutations, thereby paving the way for future research in this area.