Canine and human rabies vaccination in Colombia began at the National Institute of Health in the second decade of the 20th century. The National Veterinary School (the National University of Colombia) also contributed to the vaccination and diagnosis of canines, in addition to the diagnosis of rabies in wildlife. A combination of international cooperation and, from the 1960s onwards, increased funding of several national institutions to support the production of animal vaccines served to further progress rabies research, vaccination campaigns and diagnosis in Colombia. The country’s success in controlling canine-transmitted rabies, resulting in an approximately 90% reduction in national human rabies cases, was recognised throughout the Americas; consequently, the activities were modelled in other nations of the region. Additionally, the Ministry of Health played a key role in controlling bovine outbreaks to minimise infection risk in animal carcasses for human consumption in northern Colombia. However, in 2000, the public laboratories for vaccine production for humans and animals were closed, creating a gap in cost-effective disease control strategies in the country. In reviewing the history of rabies control in Colombia through a One Health approach, we present some lessons learned and propose improvements for the country’s long-term rabies vaccination programmes through the integration of human and animal (both domestic and wild) activities in vaccine production and roll-out. Furthermore, we highlight the importance of engaging various government, academic, private, non-government agencies and general public stakeholders in rabies control and prevention programs, especially those in remote rural settings. Finally, we present a proposal to create the national One Health Strategic Action Plan to support the operationalization of a cross-sectoral integrated zoonoses control programme in Colombia.