Background: Feeding a newborn infant with his or her mother's breast milk only or from a wet nurse without giving other liquids up to the age of 6 months is called exclusive breastfeeding (EBF). The promotion of EBF for the first 6 months of infant's life is the most effective way to reduce morbidity and mortality, especially in low- and medium-income countries. Despite several efforts to promote EBF, its practice has remained poor in many Sub-Saharan African countries including Nigeria. EBF practice is to a large extent influenced by the maternal knowledge and attitudes as well as sociodemographic and cultural factors. Objective: To determine the knowledge, acceptance, and practice of EBF among caregivers in Aminu Kano Teaching Hospital, Kano, Nigeria. Methods: This was a cross-sectional, descriptive study involving mothers who were currently breastfeeding at the time of the study or who had stopped breastfeeding not later than 2 years. Questionnaires were administered to breastfeeding mothers or fathers who knew the breastfeeding attitude of their wives during visits to the outpatient unit or immunization clinic. The age, sex, educational status, occupation, awareness, understanding of EBF, acceptance, practice, and benefits of EBF, and distance from health facility were explored from the caregivers. Results: Two hundred and seventy caregivers were studied of which 30 (11.1%) were male and 240 (88.9%) were female. The male-to-female ratio was 1:8 and the age ranges from 19 to 60 years with a mean of 29.4 and standard deviation of ±7.36. Majority of the caregivers (134, 49.6%) had tertiary level of education, while 79 (29.3%) had secondary education. Majority of the caregivers had good awareness and perception of EBF (77% and 51.5%, respectively). The EBF practice rate among the respondents was 68.52%. Caregivers with tertiary and secondary levels of education had good awareness and perception of EBF (χ2 = 48.628, P = 0.000; and χ2 = 49.106, P = 0.000, respectively). They also had good acceptance and practice of EBF (χ2 = 35.897, P = 0.000; and (χ2 = 17.999, P = 0.001, respectively). There were more awareness and perception of EBF among health workers and teachers (χ2 = 33.972, P = 0.000; and (χ2 = 12.925, P = 0.005, respectively). They also accepted and practiced EBF significantly (χ2 = 16.867, P = 0.001; and χ2 = 16.736, P = 0.001). Proximity to health facility had a significant impact on awareness, acceptance, and practice of EBF by the caregivers (χ2 = 17.391, P = 0.002; χ2 = 14.263, P = 0.007; and χ2 = 9.802, P = 0.044, respectively). Conclusion: Educational level, occupation, and proximity to health facility have positive impact on awareness, perception, acceptance, and practice of EBF among caregivers in Kano. Therefore, there is need to educate and empower women and make health facilities accessible to them to support, promote, and protect EBF in our communities.