Malaria infection accounts for over 60% of outpatient visits to healthcare facilities, 30% of child fatalities, 25% of infant deaths, and 11% of maternal mortality in Nigeria. Notably, in Nigeria, children under five years of age and pregnant women are especially vulnerable to malaria-related illnesses and death. The study, therefore, seeks to assess the knowledge of malaria disease, transmission, and use of home-based prevention strategies amongst women of reproductive age group. A cross-sectional study design was employed to assess the knowledge of malaria transmission and home-based preventive practices amongst a multistage sample of 379 women of reproductive age seeking healthcare services at the public PHC facilities in South-South, Nigeria. Data was collected using an interviewer-administered semi-structured questionnaire. Descriptive and inferential analyses of data collected were carried out using the IBM SPSS version 20 software. The mean age of the respondents surveyed in this study was 32.2 (SD ± 6.9) years. Most respondents [88.4% (n = 335)] had good knowledge of malaria transmission and prevention; however, the majority were not knowledgeable about the period mosquitoes commonly enter the house (71.5%) and the peak mosquito biting period (63.1%). There were varied degrees of practice of the various malaria home-based prevention strategies. In conclusion, a significant proportion of the surveyed reproductive-age women had some grasp on the fundamental issues of malaria transmission and prevention with some identified gaps, and they used different home-based malaria prevention measures at varied degrees. Keywords: Home-based malaria preventive practices, Knowledge, Malaria transmission and prevention, Primary healthcare, Reproductive age women, South-South Nigeria.