Cadmium, a heavy metal, is a toxic environmental and industrial pollutant. Exposure to cadmium can lead to the toxic effects in a variety of tissues, also including the brain. The present study investigated the effect of cadmium exposure on the histopathology of cerebral cortex in juvenile mice. Juvenile mice were randomly divided into control, low (1.87 mg/kg), medium (3.74 mg/kg), and high (7.48 mg/kg) dose groups. After cadmium exposure by drinking water for 10 days, the cerebral cortex was obtained for histopathology studies. The medium and high dose of cadmium, rather than low dose, could induce the histopathology alterations of cerebral cortex in a dose-dependent manner. In the high-dose group, microstructure significantly showed pia mater encephali divorcing from cerebral cortex layer, serious hyperemia of blood capillary in pia mater encephali and cerebral cortex, broadening vessel peripheral clearance, a large number of eosinophil leukocyte infiltrating around blood vessel, vacuolar degeneration in part granule cells, and obviously increasing apoptotic cells. Ultrastructure obviously displayed marginalized heterochromatin, incomplete or fused nuclear membranes, broadened perinuclear space, ambiguous mitochondria cristae, decreased synaptic cleft, and fused presynaptic and postsynaptic membrane. Our results revealed that cadmium at the middle and high dose could induce obvious microstructure and ultrastructure alterations of cerebral cortex in juvenile mice, which may be one important mechanism of cadmium neurotoxicity.