Abstract Background Necrotizing enterocolitis (NEC) is a devastating disease in preterm infants with significant morbidities, including neurodevelopmental impairment (NDI). This study aimed to investigate whether NEC is associated with (1) brain volume expansion and white matter maturation using diffusion tensor imaging analysis and (2) NDI compared with preterm infants without NEC. Methods We included 86 preterm infants (20 with NEC and 66 without NEC) with no evidence of brain abnormalities on trans-fontanelle ultrasonography and magnetic resonance imaging at term-equivalent age (TEA). Regional brain volume analysis and white matter tractography were performed to study brain microstructure alterations. NDI was assessed using the Bayley Scales of Infant and Toddler Development-III (BSID-III) at 18 months of corrected age (CA). Results Preterm infants with NEC showed significantly high risk of motor impairment (odds ratio 58.26, 95% confidence interval 7.80–435.12, p < 0.001). We found significantly increased mean diffusivity (MD) in the splenium of corpus callosum (sCC) (p = 0.001) and the left corticospinal tract (p = 0.001) in preterm infants with NEC. The sCC with increased MD showed a negative association with the BSID-III language (p = 0.025) and motor scores (p = 0.002) at 18 months of CA, implying the relevance of sCC integrity with later NDI. Conclusion The white matter microstructure differed between preterm infants with and without NEC. The prognostic value of network parameters of sCC at TEA may provide better information for the early detection of NDI in preterm infants.