Objective Sun exposure is a primary preventable risk factor for skin cancer. Sunscreen has been shown to reduce the risk of certain skin cancers such as squamous cell carcinoma and melanoma. We aimed to assess the prevalence and predictors of sunscreen use among medical students in Karachi. Methods A multi-center cross-sectional study was conducted among 578 students from multiple medical universities in Karachi, Pakistan. The levels of use of sunscreen were recorded using a comprehensive questionnaire consisting of 29 questions. Descriptive statistics were used and p-values less than 0.05 calculated using the chi-square test were considered significant. Results A majority (n=441, 73.9%) of the participants in this study were female students. Sunscreen use was prevalent in 415 (69.5%) participants. Female students were more aware of the risk of skin cancer from extended sun exposure (n=186, 72.4%). Sunscreen use was significantly associated with gender (p<0.001) and the propensity to get sunburned easily (p=0.001). Few (n=19, 5.0%) students reported being well-versed regarding skin cancer and its risk factors. Most participants were aware of the use of sunscreen for sunburn prevention (n=473, 79.2%), though knowledge of the additional benefits of sunscreen, such as the prevention of skin cancer (n=257, 43.0%) and aging (n=199, 33.3%), was lacking. Conclusion There is an evident lack of knowledge of the importance of sunscreen protection among medical students, particularly regarding the prevention of skin cancer and skin aging. However, an overall positive attitude was observed regarding the use of sunscreen among female students. Medical students are an imperative part of our future healthcare system and should be adequately informed on sunscreen benefits and skin cancer prevention.