Bioactivity-directed fractionation of the methanolic extract of the stem and fruits of Senna obliqua led to the isolation of two known antimycobacterial natural products, quinquangulin (1) and rubrofusarin (2). Both compounds had minimum inhibitory concentrations (MICs) of 12.0 μg/mL against Mycobacteria tuberculosis in radiometric culture. This is the first report of antimycobacterial activity associated with naphthopyrone compounds. Their structures were determined by spectroscopic means including 1D and 2D NMR techniques and further confirmed by X-ray crystallographic analysis.