Aim: The world is racing behind time to get dog-mediated human rabies eradicated by 2030. In response, Ghana has developed a rabies control strategy that awaits implementation. The Ghana chapter of Rabies in West Africa piloted a 3-year One Health rabies control programme in Suhum Municipality of the Eastern Region, Ghana. Questionnaires were administered as part of the exercise to gather information on local rabies-related perceptions and practices, with the aim of identifying knowledge, attitude, and practice gaps that may antagonise control efforts and endanger human life. Methods: A cross-sectional study was conducted from March to November 2020. The study involved 316 conveniently sampled households (individual per household) from three randomly selected sub-municipalities in Suhum Municipality. Data were analysed with IBM SPSS version 26. Results: Of the 316 households interviewed, 82% (n = 259) of respondents were aware of rabies, of which 78.8% (n = 204) were found to have good knowledge about rabies. Rabies awareness was significantly associated with age (P = 0.004), sex (P = 0.042), and level of education (P = 0.0405). Although a majority (76.8%) of dog bite victims reported to the hospital, only 7.1% practiced wound cleansing while a significant number (32.2%) were involved in several myth-laden traditional remedies. Conclusion: This study found that most of the respondents are aware and have good knowledge about rabies. However, their practices in disease prevention and control were poor. Continued and strengthened education through One-Health collaboration of stakeholders and the cooperation of the local community will be required for effective rabies control.