Background: Cancer among infants (<1 year old) has unique epidemiologic, clinical and genetic characteristics compared with cancer in older children. Nonetheless, data on secular trends in infant cancer incidence and survival in the US is sparse. Methods: Population-based data from Surveillance Epidemiology and End Results (SEER 9) was used to estimate the incidence, average annual percentage change (APC) for trends and survival of malignant neoplasm among infants from 1975-2014. Data were stratified by gender, race, registry and cancer type. Results: There were 3,437 new infant cancer cases with an overall incidence of 23.6/100,000. Neuroblastoma was the most common infant malignancy (6.5/100,000), followed by leukemia (3.8/100,000), and brain and central nervous system tumors (3.3/100,000). The incidence rate increased significantly over the observational period (APC 0.68; 95%CI 0.30-1.06; p<0.05). Variations in overall incidence rates were uneven across SEER registry geographic areas, with the lowest rates among both males and females in New Mexico. Relative to other racial distribution, rates were highest among whites. The relative survival rates improved over time for all tumors except for renal, sarcomas and germ cell and were not significantly different by gender or race. Conclusions: Cancer incidence among infants increased over time largely driven by leukemia, germ cell and sarcoma mainly among male infants. The overall survival for infant cancer has improved over the years especially since 1990 for hepatic tumors, lymphoma and leukemia. Further research is needed to explore the potential impacts of genetic, environmental, and perinatal factors for possible explanations for these increased cancer incidence trends.