Using 2020 National Survey on Drug Use and Health data (N = 27,170, age 18+), we examined associations of psychological distress with: (1) cannabis use frequency among all adults, and (2) cannabis use disorder (CUD) among cannabis users. Of all adults, 18.2% reported past-year cannabis use, 12.9% reported mild-moderate psychological distress, and 12.9% reported serious psychological distress. Greater proportions of cannabis users, especially those under age 35, reported psychological distress. Of cannabis users, 28.1% met DSM-5 CUD criteria. Multinomial logistic regression results showed that serious, compared to no, psychological distress was significantly associated with cannabis use at all frequency levels. Both mild-moderate and serious levels of distress were associated with similar elevated CUD risk (RRR = 1.57, 95% CI = 1.15-2.15 for mild-moderate distress; RRR = 1.58, 95% CI = 1.19-2.09 for serious distress) and 2-4 times higher risks of having moderate or severe, compared to mild, CUD and higher odds of having alcohol use disorder. The prevalence of CUD and other substance use/use disorder among cannabis users is concerning as are the significant associations of psychological distress with greater cannabis use frequency, CUD, and other substance use/use disorder. Younger adults especially may benefit from increased behavioral health services given their high prevalence of psychological distress, cannabis use, and CUD.