Background Tuberculosis (TB) remains a public health problem and early detection of drug resistance is crucial to prevent transmission of drug-resistant TB and avoid mortality. There is paucity of data on the prevalence and distribution of MDR-TB at the Republic of Congo. However, the challenges of establishing a robust testing program are significant. In resource limited settings there is a need to gather data to enable prioritization of actions. The objective of this study was to characterize the epidemiological profile of MDR and XDR-TB among presumptive tuberculosis patients referred to Makélékélé hospital in Brazzaville, Republic of the Congo. Methods We have conducted a cross-sectional study, including a total of 92 patients recruited at the Makélékélé hospital from October 2018 to October 2019. The socio-demographic and clinical data were collected as well as sputum samples. Rifampicin resistance was investigated using Xpert (Cepheid) and second-line TB drugs Susceptibility testing were performed by the Brucker HAIN Line Probe Assay (GenoType MTBDRsl VER 2.0 assay) method. Results From the 92 recruited patients, 57 (62%) were found positive for the Mycobacterium tuberculosis complex. The prevalence of rifampicin-resistant tuberculosis (RR-TB) was 9.8% (9/92) and importantly 2.2% were pre-XDR/XDR. Conclusion This study showed a high rate of rifampicin resistance and the presence of extensively drug-resistant tuberculosis in the study area in new patients. This study suggests early diagnosis of resistant tuberculosis should be considered using more sensitive diagnostic tools. Rapid molecular diagnostic tools such as GeneXpert need to be installed in health centers for better management of resistant tuberculosis.