The objective of this study was to explore the characteristics associated with having a limitation, which included any activities of daily living (ADL), instrumental activities of daily living (IADL), functional, or other activity limitations, among adults with asthma in the United States (US). This cross-sectional study included US adults (≥18 years) with asthma in the 2021 Medical Expenditure Panel Survey. A multivariable logistic regression model assessed the association between the following characteristics and the dependent variable (having a limitation, which included ADL, IADL, functional, or other activity limitation): age, sex, race, ethnicity, education, employment, income, marriage, exercise, smoking, pain, overall health, and mental health. The sample included 2325 (limitation n = 940, no limitation n = 1385) US adults with asthma, which represented an estimated weighted population of 37 210 236 (limitation n = 11 104 087, no limitation n = 26 106 149). In this analysis, characteristics associated with having a limitation (versus no limitation) included: age ≥65 versus 18-39 years (odds ratio (OR)=6.6, 95% confidence interval (CI)=3.8-11.4), age 40-64 versus 18-39 years (OR = 2.4, 95% CI = 1.5-3.9), unemployed versus employed (OR = 2.6, 95% CI = 1.7-4.0), low versus middle/high income (OR = 1.5, 95% CI = 1.0-2.2), not married versus married (OR = 1.8, 95% CI = 1.2-2.7), smoker versus non-smoker (OR = 3.0, 95% CI = 1.7-5.3), quite a bit/extreme versus little/moderate pain (OR = 2.8, 95% CI = 1.8-4.3), fair/poor versus good overall health (OR = 3.3, 95% CI = 2.0-5.3), and fair/poor versus excellent/very good overall health (OR = 6.3, 95% CI = 3.5-11.4). In conclusion, these findings offer some insight into having a limitation among US adults with asthma, although a future prospective study is needed to establish evidence of causality.