In rabies endemic areas, appropriate management of dog bites is critical in human rabies prevention. Victims must immediately wash bite wound for 15 minutes with water, soap, and a disinfectant before seeking medical care. This study investigated the epidemiology of dog bites and the determinants of compliance to these pre-clinical guidelines requirements among dog bite victims from high rabies-burden areas of Wakiso and Kampala, Uganda. An explanatory sequential mixed-methods study design was used. Quantitative data were collected from 376 dog-bite patients at two healthcare facilities. Qualitative data were also collected through 13 in-depth interviews with patients, healthcare workers, herbalists, and veterinarians. Qualitative data were analyzed using a deductive thematic approach. Generalized linear models were used to determine factors associated with compliance. Nearly half (190, 51%) of the patients were from Wakiso District and 293 (77.9%) had grade II wounds. Most of the wounds (171, 45.5%) were on the legs. Two-thirds of the bites occurred in public places. Only 70 (19%) of the bite patients had complied with pre-clinical guidelines. Nearly half of the patients had applied substances that were not recommended e.g. herbs (47/193), antiseptics (46/193), "black stone" (25/193), and unknown creams (10/193). Factors negatively associated with compliance included: being aged 15 years or older, adjPR = 0.70 (0.47-0.92) and knowing the dog owner, adjPR = 0.65 (0.36-0.93). However, attainment of secondary or higher education, adjPR = 1.76 (1.24-3.79), being in employment, adjPR = 1.48 (1.09-2.31), perception that the dog was sick, adjPR = 1.47 (1.02-2.72) and knowledge about the dog's subsequent victim(s) adjPR = 0.35 (0.17-0.70) were positively associated with compliance. High occurrence of dog bites in public places by free-roaming dogs suggests the need for deliberate promotion of responsible dog ownership. Additionally, targeted health education may be required to improve the low compliance to pre-clinical guidelines.