Fil: Brynildsrud, Ola B. Norwegian Institute of Public Health. Division of Infectious Diseases and Environmental Health; Noruega.Fil: Pepperell, Caitlin S. University of Wisconsin-Madison. School of Medicine and Public Health. Department of Medicine. Division of Infectious Disease; Estados Unidos.Fil: Suffys, Philip. Oswaldo Cruz Institute. Laboratory of Molecular Biology Applied to Mycobacteria; Brasil.Fil: Grandjean, Louis. Imperial College London. Department of Paediatric Infectious Diseases; Reino Unido.Fil: Monteserin, Johana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Debech, Nadia. Norwegian Institute of Public Health. Division of Infectious Diseases and Environmental Health; Noruega.Fil: Bohlin, Jon. Norwegian Institute of Public Health. Division of Infectious Diseases and Environmental Health; Noruega.Fil: Alfsnes, Kristian. Norwegian Institute of Public Health. Division of Infectious Diseases and Environmental Health; Noruega.Fil: Pettersson, John O-H. Norwegian Institute of Public Health. Division of Infectious Diseases and Environmental Health; Noruega.Fil: Kirkeleite, Ingerid. Norwegian Institute of Public Health. Division of Infectious Diseases and Environmental Health; Noruega.Fil: Fandinho, Fatima. Centro de Referência Professor Hélio Fraga. Laboratorio de Bacteriologia da Tuberculose; Brasil.Fil: Silva, Marcia Aparecida da. Centro de Referência Professor Hélio Fraga. Laboratorio de Bacteriologia da Tuberculose; Brasil.Fil: Perdigao, Joao. Universidade de Lisboa. Instituto de Investigação do Medicamento. Faculdade de Farmácia; Portugal.Fil: Portugal, Isabel. Universidade de Lisboa. Instituto de Investigação do Medicamento. Faculdade de Farmácia; Portugal.Fil: Viveiros, Miguel. Universidade Nova de Lisboa. Instituto de Higiene e Medicina Tropical. Unidade de Microbiologia Medica; Portugal.Fil: Clark, Taane. London School of Hygiene and Tropical Medicine. Faculty of Infectious and Tropical Diseases; Reino Unido.Fil: Caws, Maxine. Liverpool School of Tropical Medicine. Department of Clinical Sciences; Reino Unido.Fil: Dunstan, Sarah. University of Melbourne. Peter Doherty Institute for Infection and Immunity; Australia.Fil: Thai, Phan Vuong Khac. Pham Ngoc Thach Hospital for TB and Lung Diseases; Vietnam.Fil: López, Beatriz. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Ritacco, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Kitchen, Andrew. University of Iowa. Department of Anthropology; Estados Unidos.Fil: Brown, Tyler S. Massachusetts General Hospital. Division of Infectious Diseases; Estados Unidos.Fil: van Soolingen, Dick. National Institute for Public Health and the Environment. Center for Infectious Disease Research, Diagnostics and Perinatal Screening; Países Bajos.Fil: O'Neill, Mary B. University of Wisconsin-Madison. School of Medicine and Public Health. Department of Medical Microbiology and Immunology; Estados Unidos.Fil: Holt, Kathryn E. London School of Hygiene and Tropical Medicine. Faculty of Infectious and Tropical Diseases; Reino Unido.Fil: Feil, Edward J. University of Bath. Milner Centre for Evolution. Department of Biology and Biochemistry; Reino Unido.Fil: Mathema, Barun. Columbia University. Mailman School of Public Health; Estados Unidos.Fil: Balloux, Francois. University College London. University College London Genetics Institute; Reino Unido.Fil: Eldholm, Vegard. Norwegian Institute of Public Health. Division of Infectious Diseases and Environmental Health; Noruega.On the basis of population genomic and phylogeographic analyses of 1669 Mycobacterium tuberculosis lineage 4 (L4) genomes, we find that dispersal of L4 has been completely dominated by historical migrations out of Europe. We demonstrate an intimate temporal relationship between European colonial expansion into Africa and the Americas and the spread of L4 tuberculosis (TB). Markedly, in the age of antibiotics, mutations conferring antimicrobial resistance overwhelmingly emerged locally (at the level of nations), with minimal cross-border transmission of resistance. The latter finding was found to reflect the relatively recent emergence of these mutations, as a similar degree of local restriction was observed for susceptible variants emerging on comparable time scales. The restricted international transmission of drug-resistant TB suggests that containment efforts at the level of individual countries could be successful.