Background: In recent times, the novel coronavirus disease is one of the most challenging public health burdens. Low-and-middle-income countries including Ghana have not been spared by the infection. Several measures are being undertaken by countries to control and prevent the future waves of the disease. Previous studies have established the importance of knowledge, attitude and practices towards an infection as a remedy for controlling the spread of such infection. However, further studies are required to ascertain the socio-demographic characteristics influencing the knowledge, attitude and preventive measures of COVID-19. Methods: This study investigated the socio-demographic characteristics influencing knowledge, attitude and preventive practices towards COVID-19 among the Ghanaian population. A cross-sectional design was adopted to recruit 369 participants for the study utilizing convenience and snowball sampling methods. With the use of an electronic semi-structured questionnaire and social media platforms, an online survey was conducted from March 26 to May 1, 2020. Descriptive statistics, independent t-test, chi-square test, one-way analysis of variance (ANOVA) and linear regression were used to analyze data. Results: The average mean percentage of good knowledge, positive attitudes and good preventive practices regarding the novel coronavirus disease was 83.2%, 88.2% and 69.2%, respectively. In relation to occupation, there was significant difference (t = -2.984, p-value = 0.0030) in COVID-19 knowledge. Income level was significantly associated with attitudes towards COVID-19. Male gender (vs female, β = -1.276, p-value = <0.00001), less than ¢500 income earners (vs above ¢1000, β = -0.845, p-value = 0.017) were associated with lower COVID-19 preventive practice score while being the 42-64 age category (vs 18–25-year group, β = 1.128, p-value = 0.028), health worker (vs non-health worker, β = 0.816, p-value = 0.001) and belonging to Ga ethnic group (vs Akan ethnic group, β = 0.89, p-value = 0.027) were associated with higher scores. Conclusion: Although this study found higher knowledge and attitudes toward the novel coronavirus disease, it did not reflect in higher preventive practices towards the infection. In our fight against this infection in Ghana, COVID-19 preventive measure educational campaigns targeting the male gender and low-income earners should be considered and implemented.