In Murmansk oblast, the first molecular-genetic studies of circulating strains of Mycobacterium tuberculosis were carried out during the years of an increase in the incidence of tuberculosis (TB) (2003–2006). The study’s aim was to carry out a genotypic characterization of the M. tuberculosis population in Murmansk oblast and analysis of changes in its structure over 15 years. Sixty-seven M. tuberculosis strains from patients with TB newly diagnosed in 2017 were studied. The strains were assigned to the Beijing genotype and its major clusters based on analysis of specific markers. The Beijing strains were typed by 24 MIRU–VNTR loci. All non-Beijing strains were subjected to spoligotyping. Genotypes of M. tuberculosis were identified: Beijing (52.2%), Ural (19.4%), T (9.0%), LAM (7.5%), Haarlem (3.0%), and X (1.5%). Among Beijing strains, the Central Asian/Russian cluster with heterogeneous MIRU–VNTR profiles was predominant—34.3% (23/67). Multiple drug resistance (MDR)—resistance to rifampicin and isoniazid caused by mutations rpoB Ser-531Leu (TCG → TTG) and katG Ser315Thr (AGC → ACC)—was detected in 26.9% of the strains; the largest proportion of MDR strains were found in the Beijing B0/W148 cluster (85.7%), represented mainly by the MIRU–VNTR profile 100-32. High levels of clustering of Beijing Central Asian/Russian (CR = 0.68) and B0/W148 (CR = 0.71) strains reflect their current dissemination. In 2003–2017, a steady dominance of the Beijing genotype with a tendency to an increase from 44.0 to 52.2% was observed. The proportion of MDR strains in the cluster B0/W148 Beijing increased by 3.5 times, which indicates the selection and accumulation of this epidemiologically and clinically unfavorable variant of the tuberculosis pathogen in Murmansk oblast.