Neurexin 1 (NRXN1) is a synaptic adhesion molecule which is highly conserved evolutionarily. Heterozygous copy number variants in the NRXN1 gene wherein large deletions are present are associated with a variety of neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD) and schizophrenia (SCZ). NRXN1 is essential for synapse specification and function, which ultimately contributes to the balance of excitatory to inhibitory signaling (E/I ratio) in the brain. E/I signaling is thought to be a pillar of ASD pathology, but to date limited human models of ASD have been studied, and animal models may not fully recapitulate human pathology as there are several distinctions between human brains and those of common workhorse animal models. To address this here, novel ASD patient induced pluripotent stem cells (iPSCs) were sex matched with control iPSCs and differentiated into 2D neuronal cultures containing 80% glutamatergic induced neurons (Ngn2 iNs) and 20% GABAergic neurons (A/D iNs) on mouse glia. Synaptic signaling deficits were then compared across ASD and SCZ NRXN1 CNV carrier patient lines. ASD models uniquely exhibited increased glutamatergic signaling with evidence of dysregulated mitochondrial and ribosomal activity, elucidating disorder-specific pathological drivers of ASD.