Background The use of psychoactive substances is a public health challenge among young people in informal settlements. Though rarely examined, the use of psychoactive substances is linked to sexual expectancies and inhibitions, and consequently high-risk sexual behaviours. This study examined the association between sexual expectancies and inhibitions on high-risk sexual behaviours among young psychoactive substance users (PSU) in the informal settlements of Kampala, Uganda.MethodsThis cross-sectional study recruited 744 young PSU in the informal settlements of Kampala. Data were analysed using Stata 14 software. A ‘modified’ Poisson regression model was used for inferential statistics. Results Of the 744 study participants, 45.6% believed that psychoactive substance use improves sexual performance; 43.3% believed that psychoactive substances make sex more pleasurable; while more than half (53.3%) believed that psychoactive substances give courage or confidence to approach a partner for sex. The belief that psychoactive substance use improves sexual performance (PR 1.14, 95% CI: 1.01-1.30), increases the likelihood of engaging in sex (PR 1.20, 95% CI: 1.04-1.40) or gives courage or confidence to approach a sexual partner (PR 1.21, 95% CI: 1.05-1.39) were positively associated with ever having sex while under the influence of psychoactive substances. The belief that a psychoactive substance user, under the influence of psychoactive substances is more likely to engage in sex (PR 1.48, 95% CI: 1.15-1.90), and likely to find it difficult to refuse sex (PR 1.28, 95% CI: 1.06-1.55) were positively associated with engaging in multiple sexual partnerships. The belief that one easily forgets to use a condom when under the influence of psychoactive substances, was positively associated with inconsistent condom use (PR 1.26, 95% CI: 1.09-1.45).Conclusion Psychoactive substance use expectancies such as the belief that psychoactive substances improve sexual performance, and give courage or confidence to approach a sexual partner, and inhibitions such as an increased likelihood of engaging in sexual intercourse, finding difficulties in refusing to engage in sexual intercourse, and forgetting to use condoms while intoxicated predicted high-risk sexual behaviours among young PSU. Therefore, is essential to implement sexual and reproductive health and risk reduction interventions targeting young PSU in informal settlements.