Background: Tuberculosis (TB) case notifications among men outnumber those among women, yet sex disparities in TB burden and access to care are not well-understood. Methods: Systematic reviews, meta-analyses, and mathematical modelling were utilised to estimate sex disparities in TB burden and access to care, to identify drivers of those disparities in Viet Nam and Malawi, to explore sex-specific factors underlying those drivers, and to quantify the potential epidemiological impact of sex-specific strategies to further improve access to care in Viet Nam. Results: The prevalence of bacteriologically positive TB was twice as high in men as in women in low- and middle-income countries, and gaps in detection and reporting were 50% higher among men. Sex disparities in Viet Nam and Malawi were attributable to higher TB incidence and untreated disease duration in men, the latter being a year longer than in women. Sex-assortative mixing patterns that emerge in adulthood likely contribute to men’s higher incidence. Future interventions to improve access to diagnosis and treatment were projected to be most effective at reducing the epidemiological burden of TB in men, women, and children when rates of access to TB care improved in both men and women as a result of those interventions. Conclusion: Men have a higher epidemiological burden of TB and less access to care than women due to a complex nexus of biological and socio-cultural factors. Global strategies and national TB programmes should recognise men as a key affected population and prioritise men’s access to care in order to reduce TB morbidity and mortality in men, women, and children.