Sensation seeking, a personality trait, has been shown to predict engagement in high-risk behaviors. However, little is known regarding the impact of sensation seeking on substance use among street youth. We therefore sought to modify a sensation seeking scale (SSS) for use among this population. Street youth from the Vancouver-based At-Risk Youth Study (n = 226) completed the modified SSS. Exploratory and confirmatory factor analysis (EFA/CFA) were undertaken to establish the scale's dimensionality and internal validity. The association between SSS score and injection-related behaviors was tested using generalized estimating equation analysis. EFA results indicated scale unidimensionality. The comparative fit index (CFI) suggested acceptable fit (CFI = 0.914). In multivariate analysis, sensation seeking was independently associated with injection drug use, crystal methamphetamine use, polysubstance use, and binge drug use (all p < 0.05). Our findings provide preliminary support for the use of the modified SSS among street youth.