Although extreme weight control behavior (EWCB) is associated with substance use, no research has examined the association between the nonmedical use of prescription drugs (NMUPD) and EWCB. Self-report data were collected from a sample of 4,148 students in Grades 9–12 enrolled in 5 high schools across the United States. Logistic regression models were constructed to examine the nonmedical use of prescription pain relievers, depressants, stimulants, and a composite measure for any NMUPD, and the EWCB of fasting, use of diet pills, powders, or liquids, and vomiting or laxative use. Models were estimated before and after controlling for key covariates for males and females. Approximately 16% of respondents reported any EWCB during the past 30 days, while 11% reported any NMUPD during the past 30 days. After covariate adjustment, any NMUPD was associated with any EWCB in both males and females (p < .05), and all EWCB remained significant in females who reported prescription pain reliever use (p < .01), with 2 out of 3 remaining significant for prescription stimulant and depressant use (p < .01). The only significant association detected for males was between prescription pain reliever use and using diet pills, powders, or liquids (OR = 2.2, p < .01). Results suggest significant associations between NMUPD and EWCB, with variations by sex. These findings provide directions for additional research and point to several potential identification and intervention efforts.