BackgroundMusculoskeletal disorders (MSKDs) present a significant burden to health care systems worldwide. Evidence suggests that university students may have unique risk factors for developing MSKDs; however, research on the corresponding prevalence and risk factors of MSKDs in Canadian students is limited.MethodsUsing a multi-year cross-sectional survey, we aimed to understand the prevalence and risk factors of MSKDs in students at McMaster University. A survey on the prevalence of MSKD as well as potential risk factors was conducted online in the years 2018–2022. Our outcomes were the prevalence of MSKDs over the last 7 days and the last 12 months, as well as presence of lower body, upper body, and spine MSKDs. We investigated risk factors using negative binomial regression analysis, including a sex-stratified analysis.ResultsThere were a total of 289 respondents in 2018 with a decrease in the number of participants in the subsequent years (n2019= 173, n2020= 131, n2021= 76). Participants reported a median of 2–3 pain sites in the last year and 1–2 pain sites in the last week in all four years. The most prevalent sources of self-reported pain were the lower back and neck. Depending on the year and outcome studied, 59–67% of participants reported neck/lower back pain in the last year, and 43–49% reported it in the last week. Although risk factors were different depending on the year and sex, overall, poorer mental health, being in health care studies, regular sports participation (males only), older age, and less hours of sleep were significantly associated with higher prevalence of MSKDs.ConclusionsThis study identified that MSKDs are a prevalent source of pain in university students. While some risk factors, such as mental health, are known to play a role in developing MSKDs, sports activity and academic pressure are risk factors that are unique to students. Our study also suggests that there may be differences in risk factors between sexes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12891-023-06630-4.