One of the sectors that have been greatly affected by the 2019 pandemic coronavirus disease (COVID-19) was the various universities in Ghana. Universities were closed down for several months until strategically academic work resumed normalcy. COVID-19 immunisation is one of the best approaches to mitigate the spread of the novel disease. This process will increase the immunity of the students due to the extremely congested environments. For that matter, this study utilised a cross-sectional survey to assess the knowledge and attitudes of students toward vaccines in several Ghanaian universities. Reasons behind the refusal and acceptance of the COVID-19 vaccines were also ascertained. Descriptive, one-sample t-test and multinomial logistics regression statistics were used to analyse the data. Seven hundred and eighty-five (785) students from various universities in Ghana participated in this study. Respectively, 78.5% and 73.8% of the students were well informed about COVID-19 disease and COVID-19 vaccines. It can be concluded that information on social media significantly discouraged students from the COVID-19 immunisation process. The majority of students representing 63.1% were willing to receive the COVID-19 immunisation, compared to 36.3% of the students that exhibited negative attitudes toward the immunisation. The primary cause of non-compliance with the government-recommended immunisation schedule was the safety and side effects of the vaccines. It is recommended that additional advocacy initiatives be implemented at various universities to help address the numerous safety concerns students have regarding the COVID-19 immunisation and its side effects.