Introduction: In 2019, we investigated the profile of the cases and controls and the determinants of pertussis transmission in Kebbi State, Northwestern Nigeria, to inform better immunization and surveillance strategies. Methods: Community-based unmatched case–control study and review of the 2019 pertussis routine surveillance data in the affected settlements in the state were conducted. A total of 52 suspected cases of pertussis and 107 control from two local government areas in Kebbi State were recruited. Data were analyzed using descriptive and inferential statistics. Results: The highest attack rate was observed among between 1- and 4-year age group followed by children less than 1-year old, and the least attack rate was among those above 15 years. The overall attack rate and the case fatality rate were 2.10% and 0.10%, respectively. A higher attack rate was observed among women, whereas the case fatality rate was more among males. From the community survey, we observed that the cases were less likely to have pertussis vaccination history (adjusted odds ratio = 0.28, 95% confidence interval = 0.11–0.74) compared with the controls. Knowing pertussis prevention methods were found protective for pertussis transmission (adjusted odds ratio = 0.14, 95% confidence interval = 0.04–0.45). Conclusion: This study showed the vulnerability of children under 5 years, especially under 1 year, to vaccine-preventable diseases in rural populations, where “real” immunization coverage is sub-optimal, and the dominant socio-demographic factors are supportive of disease transmission. We found immunization and knowledge of the preventive measures to be protective against pertussis outbreaks. Therefore, routine immunization services must be intensified to improve coverage and prevent future pertussis outbreak(s).