Tobacco use delivers nicotine, tobacco-specific nitrosamines (TSNAs), volatile organic compounds (VOCs), and polycyclic aromatic hydrocarbons (PAHs), which are metabolized and excreted in urine offering useful biomarkers of exposure. Previous studies compared individual toxicants across tobacco users. Based on a group of biomarkers, cluster analysis was used to define tobacco toxicant exposure profiles. Clusters with distinct exposure profiles, were determined and described, based on levels of urinary biomarkers of exposure to nicotine, TSNAs, VOCs, and PAHs among a national sample of current, established, adult tobacco users, and examine the association of use behavior and cluster membership. The PATH Biomarker Wave 1 data were analyzed. Current established tobacco users with complete urinary biomarker data were included (N = 6724). User groups included cigarette smokers, users of electronic cigarette (ECIG), smokeless tobacco (SLT), and dual and poly tobacco users. Cluster analysis, pairwise comparisons, and multinomial logistic regression were conducted. Cigarette smokers were primarily in clusters with high biomarker concentrations across all groups, but actual concentrations were associated with smoking quantity. A cluster with high TSNAs but low levels of PAHs and VOCs was heavily populated by SLT users. Exclusive ECIG users, depending on use frequency, were predominantly in clusters with low biomarker concentrations, except for one cluster that had relatively high TSNAs. Clusters heavily populated by dual and poly tobacco users were the same as those heavily populated by cigarette smokers. Ten exposure profiles (clusters) were determined and linked to tobacco use behavior. Findings could inform future research and policy initiatives.