Illicit drugs and other substances are serious threats to global health and security. Thus, there have been several global efforts to enact and enforce strict humane drug laws and adequate interventions to curb the trade and use of drugs. Nevertheless, there is a dearth of research in the area of knowledge, perception, and attitude of high-risk populations, like West African university students, to guide interventions and the implementation of drug laws. In this study, we explored the knowledge, perception, and attitude of university students regarding available illicit drugs and drug users in Ghana. Adopting a cross-sectional correlational design, our results from 562 students showed that a large proportion of Ghanaian students were aware of the widely used drugs. The majority of our participants reported having heard of alcohol, cocaine, and heroin. However, fewer people reported knowing drugs such as lysergic acid diethylamide (LSD). We observed that university students in Ghana shared positive attitudes towards drug users. Participants in our study viewed drug users and problem drug users as victims who needed support rather than criminals needing punishment. Future research is required among mental health service providers and law enforcement agencies to explore their knowledge, attitude, and perception of drug users and other related issues.