Illicit drug use among adolescents has become a public health issue in Malaysia. This study was from the Global School-Based Student Health Survey (GSHS) and aimed to determine the prevalence of and factors associated with illicit drug use among school-going adolescents in Malaysia. A 2-stage stratified cluster sampling method was used and data were collected via a self-administered questionnaire. A total of 25 507 students participated in the study. The prevalence of adolescents who ever used illicit drugs was 1.7%. Adolescents who ever used illicit drugs were associated with current smoking (adjusted odds ratio [aOR] = 6.99; 95% CI = 5.19, 9.40), current alcohol use (aOR = 4.63; 95% CI = 3.43, 6.26), ever having sex (aOR = 4.76; 95% CI = 3.54, 6.41), truancy (aOR = 1.43; 95% CI = 1.07, 1.90), lack of peer support (aOR = 1.47; 95% CI = 1.07, 2.03), and lack of parental monitoring (aOR = 1.71; 95% CI = 1.22, 2.39). Public health intervention should be addressed to prevent illicit drug used among adolescents.