Sexual minority populations experience a higher burden of mental health and substance use/misuse conditions than heterosexual comparators—a health inequality that has predominantly been attributed to forms of minority stress experienced by the former group. Sexual minority-affirming legislative and policy advances, as well as improvements in social attitudes toward sexual minorities in recent decades, should presumably reduce experiences of minority stress, thereby attenuating these disparities. We conducted temporal trend analyses of annual prevalence of anxiety, depression, poor self-rated mental health, and cigarette smoking, stratified by sexual orientation and gender/sex subgroups using the Canadian Community Health Survey, 2003–2020. Descriptive analyses were used to display temporal trends; joinpoint regression was used to identify significant changes in prevalence data during 2003–2020; and prevalence ratios were estimated by year to detect any reduction in disparities. The prevalence of self-rated mental health and mood and anxiety disorders increased, whereas the prevalence of smoking decreased, between 2003 and 2020, among both sexual minority and heterosexual people in Canada. We observed a significant inflection point in 2009 in the self-rated mental health trend among bisexual women, where rates of poor mental health initially decreased from 2003 but then increased drastically from 2009 to 2020. Significant inflection points in current smoking trends were observed in 2012 among bisexual and heterosexual women and in 2013 among heterosexual men; in all three groups, both segments demonstrated decreasing trends, however, the slope of the trend became more pronounced in the latter period. Consistent with other North American studies, we found that relative differences between sexual minority and heterosexual groups for all four outcomes remained the same or increased during this 18-year period. Findings highlight the need to better understand mechanisms bolstering sexual orientation health disparities.