Background: Tobacco use is known to worsen asthma management. No studies have investigated how trends in youth tobacco use and related harm perceptions vary by asthma status and sex. This study examined these trends among Florida high school students during 2012-2018. Methods: Data from the 2012, 2014, 2016, and 2018 Florida Youth Tobacco Survey were analyzed. Public high school students (grades 9-12) with known asthma status were included along with their current tobacco product use, tobacco product harm perceptions, and demographics. Weighted multivariable logistic regression was used to assess trends in tobacco product use and harm perceptions and test differences by asthma status and sex. Results: From 2012 to 2018, high school students with asthma had the slowest decline in cigarette and cigar use prevalence (asthma status-time interaction p = 0.01) compared to those with no asthma. Cigarette and cigar smoking were perceived as less harmful over time, except among females with asthma who smoked cigarettes (p < 0.05). Conclusions: Those with asthma showed a slower decline and were more likely to smoke cigarettes. Results indicate that further public health efforts are needed to address tobacco use among high school students with asthma.