This study examined relations between student engagement and drug use using data obtained from the statewide biennial California Healthy Kids Survey. Latent variable modeling with confirmatory factor analysis indicated four conceptually distinct and psychometrically sound factors capturing academic motivation, school connectedness, caring relations, and meaningful participation. Further tests indicated relative invariance of the measurement models across grade (7th, 9th, and 11th) and gender. Structural equation models indicated unique prediction of drug use from the four engagement factors with academic motivation providing the largest magnitude of effect. Evidence of suppression was corrected statistically to show consistent prediction across the four constructs. The relative magnitude of regression coefficients diminished considerably with the introduction of relevant covariates. Results are discussed in terms of designing educational programs that emphasize multiple facets of engagement while at the same time also addressing pedagogical means to boost student academic motivation.