The current study aimed to investigate temporal trends of serum organochlorine pesticide (OCP) concentrations in the general United States population, approximately 30 years after the prohibition of OCP usage, by using National Health and Nutrition Examination Survey data. The least square geometric means and percent change in OCP concentrations were calculated by a survey weighted multiple linear regression model. Over 2005–2016, OCP concentrations showed significant downward temporal trends. Females had substantially higher concentrations of β-Hexachlorocyclohexane (β-HCH), p,p′-DDE and p,p′-DDT, but lower concentrations of Hexachlorobenzene (HCB) and trans-nonachlor. In addition, females had a more rapid decrease in p,p′-DDT levels over time than males. The overall OCP concentrations increased with age, and the two oldest age groups (aged 40–59 and 60+ years) had substantially lower rates of decrease than the younger age groups (aged 12–39 years). Concentrations and declines in OCPs (except for trans-nonachlor) were higher in Mexican Americans than both non-Hispanic Whites and non-Hispanic Blacks. There is a particular need for the ongoing monitoring of these banned chemicals, and measures should be taken to mitigate the exposure of vulnerable populations, including adults aged over 60, Mexican Americans, females for β-HCH, p,p′-DDE and p,p′-DDT, and males for HCB and trans-nonachlor.