Background: The burden of insulin resistance (IR) among young American adults has not been previously assessed. We evaluated (1) the prevalence and trends of IR and cardiometabolic risk factors and (2) the association between measures of adiposity and IR among adults 18 to 44 years of age without diabetes and preexisting cardiovascular disease. Methods: Cross-sectional survey data from six consecutive National Health and Nutrition Examination Survey (2007-2008 to 2017-2018) cycles were analyzed. IR was defined by the homeostatic model assessment for IR (HOMA-IR) of ≥2.5. The temporal trends of IR, cardiometabolic risk factors, and the relationship between IR and measures of adiposity were assessed using multivariable-Adjusted regression models. Results: Among 6247 young adults 18 to 44 years of age, the prevalence of IR was 44.8% (95% CI: 42.0%-47.6%) in 2007-2010 and 40.3% (95% CI: 36.4%-44.2%) in 2015-2018 (P for trend = 0.07). There was a modest association of HOMA-IR with higher body mass index (BMI), waist circumference, total lean fat mass, and total and localized fat mass (all Ps < 0.001). Participants with IR had a higher prevalence of hypertension [31.3% (95% CI: 29.2%-33.5%) vs 14.7% (95% CI: 13.2%-16.2%)], hypercholesterolemia [16.0% (95% CI: 12.4%-19.5%) vs 7.0% (95% CI: 5.8%-8.5%)], obesity [56.6% (95% CI: 53.9%-59.3%) vs 14.7% (95% CI: 13.0%-16.5%)], and poor physical activity levels [18.3% (95% CI: 16.4%-20.2%) vs 11.7% (95%CI: 10.3-13.1%)] compared to participants without IR (all Ps < 0.05). Conclusions: Four-in-10 young American adults have IR, which occurs in a cluster with cardiometabolic risk factors. Nearly half of young adults with IR are nonobese. Screening efforts for IR irrespective of BMI may be required.