This article estimates the risk of tuberculosis (TB) transmission on a typical commercial airliner using a simple one box model (OBM) and a sequential box model (SBM). We used input data derived from an actual TB exposure on an airliner, and we assumed a hypothetical scenario that a highly infectious TB source case (i.e., 108 infectious quanta per hour) travels as a passenger on an 8.7-hour flight. We estimate an average risk of TB transmission on the order of 1 chance in 1,000 for all passengers using the OBM. Applying the more realistic SBM, we show that the risk and incidence decrease sharply in a stepwise fashion in cabins downstream from the cabin containing the source case assuming some potential for airflow from more contaminated to less contaminated cabins. We further characterized spatial variability in the risk within the cabin by modeling a previously reported TB outbreak in an airplane to demonstrate that the TB cases occur most likely within close proximity of the source TB patient.