Background: Exclusive breastfeeding (EBF) is recommended for the first six months of age by the World Health Organization. Mothers' good knowledge and positive attitude play key roles in the process of exclusive breastfeeding practices. In this study, we report on a systematic review of the literature that aimed to examine the status of mothers' knowledge, attitude, and practices related to exclusive breastfeeding in East Africa, so as to provide clues on what can be done to improve exclusive breastfeeding. Methods: A systematic review of peer-reviewed literature was performed. The search for literature was conducted utilizing six electronic databases, Pub med, Web of Science, Google Scholar, Embase, Science Direct, and Cochrane library, for studies published in English from January 2000 to June 2019 and conducted in East Africa. Studies focused on mothers' knowledge, attitudes, or practices related to exclusive breastfeeding. All papers were reviewed using a predesigned data extraction form. Results: Sixteen studies were included in the review. This review indicates that almost 96.2% of mothers had ever heard about EBF, 84.4% were aware of EBF, and 49.2% knew that the duration of EBF was the first six months only. In addition, 42.1% of mothers disagreed and 24.0% strongly disagreed that giving breast milk for a newborn immediately and within an hour is important, and 47.9% disagreed that discarding the colostrum is important. However, 42.0% of mothers preferred to feed their babies for the first six months breast milk alone. In contrast, 55.9% of them had practiced exclusive breastfeeding for at least six months. Conclusions: Exclusively breastfeeding among our sample is suboptimal, compared to the current WHO recommendations. Thus, it is important to provide antenatal and early postpartum education and periodical breastfeeding counseling, to improve maternal attitudes and knowledge toward breastfeeding practices.