Prior research suggests that children with a low socioeconomic status (SES) background are at an increased risk for special healthcare needs. Conversely, for hypersensitivity-related diseases, many studies reported a lower risk among children with lower SES according to the hygiene hypothesis. We aimed to evaluate the association between SES and several hypersensitivity diseases and autism in a representative American sample. We used data from the 2016, 2017 and 2018 US National Survey of Children's Health. A total of 102,341 children aged 0-17 years were included. The dependent variables were doctor-diagnosed allergies, arthritis, asthma, diabetes, and autism. The main SES indicators were family poverty levels, highest education of the reported adults and difficulty in family income. Our analysis used logistic regression that accounted for the survey sampling design. The sample had a mean age of 9.4 ± 5.3 years. The weighted prevalence for allergies was 24.4%, 0.3% for arthritis, 11.9% for asthma, 0.5% for diabetes and 2.6% for autism. Children with adults reporting higher educational levels had greater odds of allergies (adjusted odds ratio and 95% CI: 1.48, 1.23-1.78) than those with lower educational levels. But for all other diseases, most findings suggested that a higher odds of disease was associated with lower SES instead of higher SES. A low SES background remains an important risk factor for hypersensitivity diseases in children. Most of our results suggested that children with low SES were associated with a higher risk of hypersensitivity diseases and autism.