Cannabis legalization has rapidly spread throughout the United States and is associated with multiple public health outcomes, including driving under the influence of cannabis (DUIC). To improve understanding of the relationship between legalization and DUIC, we tested two potential mediators of this relationship: perceived safety and perceived legality of driving high. We analyzed data from 1,236 current (past 30-day) cannabis users who were recruited from states with recreational, medical only, or no legal cannabis between 2016 and 2017 using address-based and social media samples. Using a generalized linear model and adjusting for cannabis legalization, demographics, living in a state with a cannabis-specific drugged driving law, frequency of cannabis use, and weights, we found that perceived safety (risk ratio [RR] = 2.60, 95% CI [1.88, 3.58]), but not perceived legality (RR = 0.96, 95% CI [0.67, 1.37]), was significantly associated with DUIC. Perceived safety mediated the relationship between legalization and DUIC (Coeff: -0.12, 95% CI [-0.23, -0.01]). Models stratified by frequency of cannabis use yielded results consistent with those of pooled models except that, for frequent users, cannabis-specific driving laws were associated with a significantly lower risk of DUIC (RR = 0.64, 95% CI [0.44, 0.92]). Agencies developing cannabis-focused drugged driving educational campaigns should consider the potential role of perceived safety of driving high in DUIC campaigns.