In total, 303 randomly selected clinical Mycobacterium tuberculosis (MTB) isolates from 303 patients (collected January to December 2012) in central Taiwan were examined. The major lineages found were Beijing (N = 114, 37.62%), Haarlem (N = 76, 25.08%) and East African-Indian (EAI) (N = 42, 13.86%). Notably, younger persons (≤30 years old) were 6.58 times more likely to be infected with a Beijing genotype compared to older persons (>70 years) (p < 0.05). Combining molecular typing methods and geographical information system (GIS) analysis, we uncovered a twofold higher incidence of Beijing strains in a hotspot area (33%) compared to non-hotspot areas (17%). By 24 MIRU-VNTR typing, persons in clustered groups were 1.96 times more likely to be infected with a Beijing strain compared with non-clustered persons, suggesting recent spread and emergence of MTB. Finally, we observed a trend in which TB incidence increased as the density/concentration of analyzed environmental factors increased, suggesting that environmental factors are associated with TB transmission; however, only population density was found to be significantly associated with increased risk of TB (p < 0.05). Molecular typing methods combined with spatial analysis suggest possible TB transmission. Early intervention to interrupt transmission may be most effective if targeted to hot zones of TB.