Five neonates with organic acidemia complicated by severe hyperammonemia were reported, including one case of isovaleric acidemia (IVA), three cases of methylmalonic acidemia (MMA), and one case of propionic acidemia (PA). The neonates were 3 to 19 days old. All presented with nonspecific symptoms such as poor feeding and decreased responsiveness, some with vomiting. All had dyspnea, and one had seizures. All cases were genetically confirmed: the IVA case carried a homozygous IVD variant, the three MMA cases carried compound heterozygous MMUT variants, and the PA case carried a homozygous PCCA variant. During the acute hyperammonemic phase, all five received N-carbamylglutamate (NCG). Two critically ill infants with peak ammonia >1 500 μmol/L underwent continuous veno-venous hemodialysis first and were started on oral NCG after ammonia fell below 200 μmol/L; the other three received oral NCG directly. Blood ammonia levels declined markedly in all cases, feeding was resumed successfully, and protein intake was gradually increased. In the chronic phase, all were maintained on oral NCG. One MMA infant died at 6 days of age due to treatment withdrawal by the family; the remaining four maintained ammonia <80 μmol/L. Over more than 12 months of follow-up, all four survivors had growth parameters (length, weight, and head circumference) within normal ranges, with two exhibiting mild delays in gross motor and language comprehension. NCG shows good safety and effectiveness for both acute rescue and long-term management of organic-acidemia-related hyperammonemia, and provides a reference strategy for clinical care.