Exclusive Breastfeeding (EBF) is recommended for 6 months of age also with continued breastfeeding for 2 years of age or beyong. Many African mothers breastfeed their babies beyond one year, but EBF for up to six months is still not widely practiced. In the Republic of Congo, according to the Congo Demographic Health Survey, the prevalence of EBF was 32.9%. The knowledge of infants’ mothers could be insufficient to motivate the latter to adopt good exclusive breastfeeding practices. Objectives The objective of the study is to assess the determinants of knowledge, attitudes and practice of breastfeeding mothers in the Talangaï district of Congo. Study design A cross sectional analytical survey was conducted. Methods A KAP analytical study was carried out from December 3, 2017, to July 15, 2018, based on the four health centers of the Talangaï health district in Congo Brazzaville. Using formula from Schwartz, 357 mothers were included. The practice of EBF was determined based on a 24-h recall.. A logistic regression analysis was performed, and the odds ratio was calculated with a 95% confidence interval. Results The mean age of mothers was 26.8 years (± 5.9 years). Mothers with 2-3 children represented 42.6% of the sample. The prevalence of EBF among infants 0–6 months old was 33.9%. Mothers' knowledge, attitudes and practices were unsatisfactory (78.4%), favourable (79.5%) and bad (67.2%), respectively. Factors associated with satisfactory knowledge were being a public official [OR: 3.18 (1.39-7.28)] and/or multiparous [OR: 2.25 (1.23-4.11)]. Mothers who had satisfactory knowledge had a higher rating of having good practices on EBF. Conclusions Factors related to good knowledge among mothers are multiparity, age and being a civil servant. Promoters’ EBF must target mothers through the media and even in the community by sensitizing them on the subject.