This study describes gender-specific patterns in alcohol and drug use among Swedish high school students throughout 2020 and questions the current cutoffs for identifying addiction in this population. From September 2020 to February 2021, 1590 Swedish upper secondary high school students (mean age 17.15 years, age range 15–19 years, 39.6% male, and 60.4% female) completed the anonymous, electronic survey of the Mental and Somatic Health without borders study. The respondents reported their substance use habits during the previous 12 months using the Drug Use Disorders Identification Test (DUDIT) and Alcohol Use Disorders Identification Test (AUDIT). They also answered questions about changes in their alcohol and illegal drug use habits after the COVID-19 outbreak. No gender differences were detected in the prevalence and degree of alcohol use. Compared to female adolescents, significantly more male adolescents used drugs (and to a significantly higher degree, although with a small effect size). Substance use problems peaked in females at age 17 and in males at age 18. The COVID-19 outbreak affected alcohol consumption and illegal drug use in male and female adolescents similarly. For both genders, of those who used illegal drugs, over 40% reported increased use after the outbreak. Our results reinforce previous suggestions of the narrowing of gender differences in Swedish adolescents’ risk behaviors and challenge the previously validated gender-specific cutoffs for the AUDIT and DUDIT. An improved understanding of the impacts of gender diversity and evolving gender roles and norms on behaviors and mental health is warranted.