Objective: The study objective was to investigate the factors associated with the physical and psychological wellness of United States (US) adults with asthma.Methods: This cross-sectional analysis used a sample of 2329 US adults with asthma in the 2021 Medical Expenditure Panel Survey data. A logistic regression model investigated the association of the following factors and the dependent variables (physical wellness and psychological wellness): age, sex, race, ethnicity, education, employment, healthcare provision, marriage, income, regular physical activity, current smoker, pain, and limitations. Nationally representative estimates were produced through a weighted analysis. The data structure was maintained using cluster and strata variables. The alpha limit was 0.05.Results: Factors associated with higher odds of reporting good physical wellness included: private (versus no) healthcare provision (odds ratio [OR] = 2.63, 95% confidence interval [CI] = 1.10–6.26), good (versus poor) psychological wellness (OR = 6.83, 95% CI = 4.35–10.72), regular (versus no regular) physical activity (OR = 2.18, 95% CI = 1.42–3.34), little/moderate (versus quite a bit/extreme) pain (OR = 3.51, 95% CI = 2.38–5.15) and no (versus any) limitation (OR = 3.73, 95% CI = 2.30–6.06). In the psychological wellness model, those aged ≥70 (OR = 6.18, 95% CI = 2.72–14.07), 60–69 (OR = 4.64, 95% CI = 2.13–10.10), and 50–59 (OR = 4.96, 95% CI = 2.24–11.02) versus those aged 18–29, and good (versus poor) physical wellness (OR = 6.89, 95% CI = 4.34–10.94) were associated with higher odds of reporting good versus poor psychological wellness.Conclusion: These results may be helpful at targeting resources to optimize the wellness of US adults with asthma. Additional studies are needed to determine any temporal associations between these findings.