Background <p>Motorcycles are a common mode of transport in Ghana, such that in some regions, they account for 90% of all registered vehicles. Their popularity and associated crash vulnerabilities have become a significant public health issue. However, there is limited knowledge of the long-term epidemiological profile of fatal crashes in Ghana. This study examines the epidemiology of fatal motorcycle crashes over a 23-year period.</p> Methods <p>We analysed 23 years of national data on motorcycle crashes. The data is collated by the Building and Road Research Institute from police-reported crash investigation files. Data were summarised for the temporal, environmental, and rider-related features of fatal crashes. A mixed-effects Poisson regression with robust variance estimation was employed to identify factors influencing fatal motorcycle crashes.</p> Results <p>Over the 23 years, 40,322 motorcycle crashes occurred, and 22.85% were fatal. Fatal crashes have increased, with an average annual percent change increase of 4.71% and 60% occurring from 2016 to 2022. The average age of the riders was 31.64 years, and 98.90% of the fatal crash riders were males. A greater proportion of fatality ratios were recorded in the northern parts Ghana (Upper West = 36.80% and Upper East = 36.60%), and during the last three months of the year (28.97%). The day of the week, time of day, weather, traffic control, road type, rider age and sex, and collision type were significant factors associated with fatal motorcycle crashes.</p> Conclusion <p>The findings emphasise a significant public health burden from motorcycles, particularly over the past 10 years. Targeted interventions (e.g., speed-control measures) are needed to address this crisis, particularly as the country prepares to commercialise its use for passenger transport.</p>