To identify prototypical developmental patterns of tobacco product and cannabis use and co-use initiation during adolescence, and determine risk factors for and consequences of these initiation patterns. Prospective repeated-measures cohort with eight semi-annual assessments during high school. Multiple-event process survival mixture modeling identified latent initiation classes with distinct patterns of variation in timing of use initiation of tobacco products and cannabis. We then estimated: (1) associations of baseline risk factors with membership in initiation classes and (2) differences between initiation classes in frequency of cannabis and tobacco product use at the final assessment. Ten high schools in the Los Angeles, CA, USA metropolitan area, 2013-17. Students [1031 (45.4%) males; mean (standard deviation) age at baseline=14.6 (0.39) years] who had never used any tobacco products or cannabis at baseline 9th grade assessment (n=2272). Self-report measures of electronic cigarette (e-cigarette), combustible cigarette, hookah, cigar/cigarillos and cannabis use were collected at each assessment. Four distinct tobacco and cannabis use initiation classes were identified: (1) early and high-risk cannabis and polytobacco initiators (n=116; 5.1%); (2) early cannabis and polytobacco initiators (n=172; 7.6%); (3) late cannabis and e-cigarette initiators (n=431; 19.0%); and (4) abstainers (n=1553; 68.4%). At baseline, older age for the early and high-risk cannabis and polytobacco initiators [odds ratio (OR)=1.22, 95% confidence interval (CI)=1.10, 1.35, P<0.001], peer cannabis use (OR=1.60, 95% CI=1.23, 2.08, P<0.001) and delinquent behavior (OR=1.30, 95% CI=1.08, 1.55, P=0.004) were associated with membership in the three initiation classes (versus abstainers). Membership in the early and high-risk cannabis and polytobacco initiators class (versus three other classes) was significantly associated with increased past 30-day frequency and daily intensity of use at the final assessment (P-values <0.001). Older age, peer cannabis use and delinquent behavior appear to be risk factors for the initiation of tobacco/cannabis product use among high school students in the Los Angeles metropolitan region. Early and higher-risk polyproduct use initiation appears to be associated with greater escalation of past 30-day and daily tobacco and cannabis use at the end of the high school.