Background Although substantial progress has been made in combating the crisis of multi-drug resistance tuberculosis (MDR-TB), it remained the major public health threat globally. Objective To assess patients’ survival and its predictors among patients receiving multi-drug resistance tuberculosis treatment at MDR-TB treatment centers of southern and southwestern Ethiopia. Methods A multicenter retrospective observational study was conducted from April 14 to May 14, 2019, among patients receiving MDR-TB treatment at three MDR-TB treatment centers, Butajira, Arbaminch and Shenengibe Hospitals, located in south and southwestern Ethiopia. A total of 200 records were reviewed using a check list adopted from the national MDR-TB treatment charts and other relevant documents. Data were entered into Epi-Data version 4.2.0 for cleaning and exported to STATA-13 for analysis. Descriptive analysis was carried out and results were presented by text, tables, and charts. Kaplan-Meier (log-rank test) and Cox regression were used to compare baseline survival experience and to determine predictors of patients’ survival (death), respectively. The adjusted hazard ratio (AHR) was used to measure the strength of association and a p-value of <0.05 was considered to declare statistical significance. Results Of 200 patients, 108 (54%) of them were males. The mean (+ standard deviation) age of the study population was 32.9±9.5years. During follow-up, 22 (11%) deaths were reported. The overall incidence density of death was 11.99, 95% CI [7.89–18.21] per 100,000person-years. The median (interquartile range (IQR)) survival time was 375(249–457) days. Comorbidity (AHR = 23.68, 95% CI [4.85–115.46]), alcohol consumption (AHR = 4.53, 95% CI [1.21–16.97]), and history of poor adherence (AHR = 12.27, 95% CI [2.83–53.21]) were independently associated with patients’ survival (death). Conclusion In this study, the incidence density of mortality was very high. Alcohol consumption, poor adherence, and the presence of comorbidity were independently associated with death. Hence, alcohol users, patients with comorbidity and poor adherence should be given due attention during therapy.