Portugal is a low incidence country for tuberculosis (TB) disease. Now figuring among TB low incidence countries, it has since the 1990s reported multidrug resistant and extensively drug resistant (XDR) TB cases, driven predominantly by two strain-types: Lisboa3 and Q1. This study describes the largest characterization of the evolutionary trajectory of M/XDR-TB strains in Portugal, spanning a time-period of two decades. By combining whole-genome sequencing and phenotypic susceptibility data for 207 isolates, we report the geospatial patterns of drug resistant TB, particularly the dispersion of Lisboa3 and Q1 clades, which underly 64.2% and 94.0% of all MDR-TB and XDR-TB isolates, respectively. Genomic-based similarity and a phylogenetic analysis revealed multiple clusters (n = 16) reflecting ongoing and uncontrolled recent transmission of M/XDR-TB, predominantly associated with the Lisboa3 and Q1 clades. These clades are now thought to be evolving in a polycentric mode across multiple geographical districts. The inferred evolutionary history is compatible with MDR-and XDR-TB originating in Portugal in the 70's and 80's, respectively, but with subsequent multiple emergence events of MDR and XDR-TB particularly involving the Lisboa3 clade. A SNP barcode was defined for Lisboa3 and Q1 and comparison with a phylogeny of global strain-types (n = 28 385) revealed the presence of Lisboa3 and Q1 strains in Europe, South America and Africa. In summary, Portugal displays an unusual and unique epidemiological setting shaped by >40 years of uncontrolled circulation of two main phylogenetic clades, leading to a sympatric evolutionary trajectory towards XDR-TB with the potential for global reach. Multidrug-resistant (MDR) tuberculosis (TB) poses a serious threat to the WHO goal of eliminating TB by 2035 1. In Europe alone, the number of MDR-TB notified cases amounted to 35 224 cases in 2017 2. MDR-TB treatment involves using second-line drugs which are more expensive, have longer treatment regimens and currently have lower success rates 1. Extensively Drug Resistant (XDR) TB, which is MDR-TB with concomitant resistance to a fluoroquinolone and an injectable second-line drug, is associated with a much worse outcome 1. Portugal recently became a low TB incidence country by reporting a notification rate below 20 cases per 100 000 habitants (17.5/100 000 in 2017) 2. Nonetheless, it still reports the highest incidence rate in Western Europe and while this rate shows a steady decline averaged at −7.9% per year, treatment success rates are decreasing. Additionally, according to the most recent data from the WHO, it is estimated that Portugal had 24 new incident cases per 100 000 habitants in 2018 1. Ten MDR-TB cases were reported in 2017, but this is thought to be an underestimate, as only 61.4% of all TB cases are laboratory-confirmed, and only 66.7% of those underwent drug