Background The rate of multidrug-resistant tuberculosis is increasing at an alarming rate throughout the world. It is becoming an emerging public health problem in East Africa. The prevalence of multidrug-resistant tuberculosis among pulmonary tuberculosis positive individuals in the region has not been thoroughly investigated. Aim The aim of this systematic review and meta-analysis is to estimate the pooled prevalence of multidrug-resistant tuberculosis among newly diagnosed and previously treated pulmonary tuberculosis cases in East African countries. Methods English published articles were systematically searched from six electronic databases: PubMed, EMBASE, Scopus, Science direct, Web of Science, and Google scholar. The pooled prevalence of multidrug-resistant tuberculosis and associated risk factors were calculated using Der Simonian and Laird’s random Effects model. Funnel plot symmetry visualization confirmed by Egger’s regression asymmetry test and Begg rank correlation methods was used to assess publication bias. A total of 16 articles published from 2007 to 2019 were included in this study. STATA 14 software was used for analysis. Results Out of 1025 articles identified citations, a total of 16 articles were included in final meta-analysis. The pooled prevalence of multidrug-resistant tuberculosis among newly diagnosed tuberculosis cases and previously treated tuberculosis patients was 4% (95%CI = 2–5%) and 21% (95%CI: 14–28%), respectively. Living conditions, lifestyles (smoking, alcohol use, and drug abuse), previous medical history, diabetes history, and human immunodeficiency virus infection were risk factors contributing to the higher prevalence of multidrug-resistant tuberculosis in East Africa. Conclusion The review found a significant prevalence of multidrug-resistant tuberculosis in the region. An early diagnosis of tuberculosis and rapid detection of drug-resistant Mycobacterium tuberculosis is a critical priority to identify patients who are not responding to the standard treatment and to avoid transmission of resistant strains. It is also very important to strengthen tuberculosis control and improve monitoring of chemotherapy.