Background: This study explores the patterns of use and co-use of tobacco and cannabis among Ontario adolescents over 3 decades and if characteristics of co-users and single substance users have changed. Methods: Co-use trends for 1981-2011 were analyzed using the Centre for Addiction and Mental Health Ontario Student Drug Use and Health Survey, which includes 38,331 students in grades 7, 9, and 11. A co-user was defined as someone reporting daily tobacco and/or cannabis use in the past month. Trends over time (by gender and academic performance) were analyzed with logistic regression. Results: The prevalence of tobacco-only use, cannabis-only use, and co-use fluctuated considerably. During 1981-1993, there were more tobacco-only users than co-users and cannabis-only users; since 1993 the prevalence of tobacco use has decreased dramatically. Co-use prevalence peaked at 12% (95% confidence interval: 9, 15) in 1999, when prevalence of overall use of both substances was highest. In 2011, 92% of tobacco users also used cannabis, up from 16% in 1991. Conclusions: In 2011 nearly all students who smoke tobacco daily also use cannabis. Non-regular use of either substance is highest now compared with the past 3 decades. Contemporary tobacco and cannabis co-users are significantly different than past users. Youth prevention programs should understand the changing context of cannabis and tobacco among youth.