Smoking prevalence is high among substance abusers, making it important to understand when nicotine abstinence will aid, impair, or not affect abstinence from other substances. This study tested novel hypotheses about the coupling of nicotine and stimulant craving over time during stimulant dependence treatment. Adults (N = 538) with cocaine and/or methamphetamine dependence completed a 10-week randomized controlled trial of substance use treatment with or without smoking cessation treatment. Participants reported nicotine and stimulant craving weekly and use twice per week. Latent change score modeling tested the association between weekly increases in nicotine craving and subsequent weekly changes in stimulant craving. Interestingly, results revealed a "substitution" effect: increases in nicotine craving predicted subsequent decreases in stimulant craving, γ = -.37, p = .001. Additionally, increases in nicotine craving predicted subsequent increases in nicotine use, γ = 1.26, p = .04, and decreases in stimulant use, γ = -.07, p = .03. As expected, the substitution effect between nicotine and stimulant craving was stronger when stimulants were administered through the same route as nicotine (i.e., smoking), γ = -.56, p = .005, versus other routes, γ = -.32, p = .06. Finally, smoking cessation treatment eliminated the coupling between nicotine craving and stimulant craving, γ = -.07, p = .39. Contrary to concerns about nicotine abstinence during substance dependence treatment, increases in nicotine craving may be associated with later reductions in stimulant craving and use, and unrelated when smoking cessation treatment is introduced. Weekly changes in nicotine craving convey information that can help clinicians to predict and understand shifts in stimulant craving and use during substance use disorder treatment.