Recent research has shown that gender is an important driver of the risk of mortality and morbidity rates for people with COVID-19, with case fatality rates being higher for women than men. Despite this pattern, research is sparse on gender risk perception and potential coping mechanisms. This study examined the role gender plays in the relationship between COVID-19 risk perception and coping mechanisms among university students. Through the adoption of traditional and online surveys, 859 students from two public universities in Ghana were conveniently selected to respond to the survey instrument. The results from the multivariate regression analysis revealed that COVID-19 risk perception was positively related to active coping. The outcome of the moderation analysis showed that while males were more likely than females to adopt active and emotional support coping with heightened risk perception, a contrary outcome was observed for behaviour disengagement. This result is an indication that female students are likely to be overwhelmed with a high level of risk perception and easily give up trying to adopt effective strategies to reduce the effect of the COVID-19 pandemic situation. The findings highlight the need for different forms of intervention for male and female students for dealing with the effect of COVID-19.