Background: Past studies have revealed the lasting effects of stress susceptibility and maternal immune activation on hippocampal DNA methylation landscape in adult offspring. Yet, alterations of the DNA methylation landscape during early postnatal development and following maternal immune activation remain less studied. Methods: We used two mouse strains characterized by social dominance (Dom) and submissiveness (Sub), exhibiting inherent traits of elevated and diminished stress sensitivity. Additionally, Poly IC was administered to a subgroup of the dams at gestational day 14 to induce maternal immune activation to explore whether stress susceptibility contributes to the heightened effects of Poly IC on DNA methylation and behavior. We explored DNMTs and TETs levels across development accompanied by reduced-representation bisulfite sequencing (RRBS-Seq) on hippocampal DNA extracted from 7-day-old Sub and Dom pups and a behavioral battery. Results: We observed significant changes in DNMTs and TETs expression and altered DNA methylation landscapes in both the intergroup comparisons of sub and dom and in sub and dom subjects exposed to Poly IC. Differentially methylated sites were enriched for genes that regulate behavior and neuronal development. These findings were associated with significant changes in exploratory behaviors and MK801-induced hyperlocomotion. Conclusion: We showed that the combination of stress susceptibility and maternal immune activation leads to unique DNA methylation patterns associated with more severe behavioral abnormality.