Background: Health warning labels (HWLs) on cigarette packs in Australia, Canada, Mexico, and the United States include varying information about toxic cigarette smoke constituents and smoking-related health risks. HWL information changed more recently in Australia, Canada, and Mexico than in the United States. Aims: To investigate whether smokers' knowledge of toxic constituents and perceived smoking-related risks increased after adding this information to HWLs and how knowledge of toxic constituents is associated with perceptions of smoking-related risks. Methods: Data come from a longitudinal, online cohort of 4,621 adult smokers surveyed every 4 months from September 2012 (Wave 1) to January 2014 (Wave 5) in Australia, Canada, and Mexico, with the United States being surveyed from Waves 2 to 5. Generalized estimating equation models estimated the association between perceived smoking-related risk at follow-up and prior wave knowledge of toxic constituents, adjusting for attention to HWLs, sociodemographics, and smoking-related characteristics. Results: Between 2012 and 2014, knowledge of toxic constituents increased in Australia, Canada, and Mexico (p < 0.001), but not in the United States. Higher levels of both attention to HWLs and knowledge of toxic constituents were associated with a higher perceived risk of smoking-related conditions at follow-up across all countries except for the United States. Conclusions: Our results suggest that information about toxic constituents on prominent HWLs not only increases smoker's knowledge of toxic constituents, but that it may also reinforce the effects of HWL messages about specific, smoking-related health outcomes.