A total of 197 Year 9 and 10 students, 74 of whom had learning difficulties (LD), from two high schools in Brisbane, the capital city of Queensland, Australia, self-reported their substance use. Seventeen substances, including two fictitious ones to detect over-reporting, were presented to participants for them to indicate their current usage, ex-usage, or non-usage. The findings revealed that participants were most likely to use alcohol, tobacco, and marijuana. A series of Chi-square (χ2) analyses found that male students with LD and female students without LD were at greatest risk of substance use, overall. These findings are discussed in the light of the previous limited research pertaining to substance use amongst students with LD.