Background and ObjectivesResearch on substance use disorder (SUD) among Muslims in the United States (US) is limited. There are several unique factors, including denial and stigma, that make this population at risk of SUD. This study explored the prevalence, treatment utilization, and impact of SUD among Muslims in the US compared with a matched control group from general respondents.MethodsData from 372 self‐identified Muslims were obtained from the National Epidemiologic Survey on Alcohol and Related Conditions III. A matched non‐Muslim control group (N = 744) were selected based on demographics and other SUD‐related clinical variables. The impact of SUD was assessed using the 12‐Item Short Form Health Survey (SF‐12).ResultsAmong the 372 Muslims, 53 (10.85%) had lifetime alcohol/drug use disorder, while 75 (18.42%) had lifetime tobacco use disorder (TUD). With statistical significance, alcohol use disorder (AUD) was lower while TUD was higher in the Muslim group than in the control group. The rates of all other substances were not statistically different between the Muslim and control groups. The Muslim group have higher help‐seeking and a lower mean score on the SF‐12 emotional scale than the control group.Conclusion and Scientific SignificanceMuslim Americans have higher prevalence of TUD, lower prevalence of AUD, and similar prevalence of other SUD compared to the public. Affected individuals have poor emotional functioning which may be exacerbated by the impact of stigma. This is the first study to estimate prevalence of variety of SUD in American Muslims from a national representative sample.