BACKGROUND: Tuberculosis is a leading infectious cause of death worldwide. Novel vaccines will be required to reach global targets and reverse setbacks resulting from the COVID-19 pandemic. We estimated the impact of novel tuberculosis vaccines in low-income and middle-income countries (LMICs) in several delivery scenarios. METHODS: We calibrated a tuberculosis model to 105 LMICs (accounting for 93% of global incidence). Vaccine scenarios were implemented as the base-case (routine vaccination of those aged 9 years and one-off vaccination for those aged 10 years and older, with country-specific introduction between 2028 and 2047, and 5-year scale-up to target coverage); accelerated scale-up similar to the base-case, but with all countries introducing vaccines in 2025, with instant scale-up; and routine-only (similar to the base-case, but including routine vaccination only). Vaccines were assumed to protect against disease for 10 years, with 50% efficacy. FINDINGS: The base-case scenario would prevent 44·0 million (95% uncertainty range 37·2-51·6) tuberculosis cases and 5·0 million (4·6-5·4) tuberculosis deaths before 2050, compared with equivalent estimates of cases and deaths that would be predicted to occur before 2050 with no new vaccine introduction (the baseline scenario). The accelerated scale-up scenario would prevent 65·5 million (55·6-76·0) cases and 7·9 million (7·3-8·5) deaths before 2050, relative to baseline. The routine-only scenario would prevent 8·8 million (95% uncertainty range 7·6-10·1) cases and 1·1 million (0·9-1·2) deaths before 2050, relative to baseline. INTERPRETATION: Our results suggest novel tuberculosis vaccines could have substantial impact, which will vary depending on delivery strategy. Including a one-off vaccination campaign will be crucial for rapid impact. Accelerated introduction-at a pace similar to that seen for COVID-19 vaccines-would increase the number of lives saved before 2050 by around 60%. Investment is required to support vaccine development, manufacturing, prompt introduction, and scale-up. FUNDING: WHO (2020/985800-0). TRANSLATIONS: For the French, Spanish, Italian and Dutch translations of the abstract see Supplementary Materials section.