Individuals pre-sensitized with Mycobacterium tuberculosis (MTB), non-tuberculosis mycobacteria, and its impact on TB incidence are relatively unexplored in a high TB burden setting. We conducted secondary data analysis of a double-blind, randomized Chengalpattu BCG trial, India. Induration to Purified Protein Derivative (PPD)-S and PPD-B were proxies for exposures to MTB and M. intracellulare respectively. Optimum cut-off for PPD-S and B were determined using Receiver-Operating Characteristic curves and induration ≥12 mm for PPD-S and ≥10 mm for PPD-B were considered strong reaction. Incidence rates of culture positive pulmonary TB per 100,000 person-years (PY) were calculated. Of 270,043 individuals with skin test results, children <14 years (n = 109,383, 64% showed strong-reaction to PPD-B and 17% to PPD-S) and adults between 25 and 34 years (n = 40,292, 98% were strong reactors to PPD-B and 73% to PPD-S). Overall incidence rate was lower in individuals with PPD-S < PPD-B (136, 95% CI: 130–141/100,000 PY) compared to individuals with PPD-S > PPD-B (447, 95% CI: 427–468/100,000 PY). Incidence rates of culture positive pulmonary TB was affected by early age of exposure to cross-reactive mycobacterial antigens represented by PPD-B and exposure to MTB represented by PPD-S during adolescence and early adulthood.