A quantitative structure activity relationship study was performed on series of substituted Mannich bases of 5- hydroxy-2-methyl-4H-pyran-4-ones and Schiff”s bases of Benzothiazole obtained from an elaborate literature survey as anti-tuberculosis compounds for establishing quantitative relationship between biological activity and their physiochemical/structural properties. In recent years, a large number of newer drugs are promoted in treatment of tuberculosis especially due to the emergence of MDR (multi drug resistant) and XDR (extensive drug resistant) tuberculosis. Theoretical results are in accord with the invitro experimental data with reported growth inhibitory activity towards Mycobacterium tuberculosis. Various physico chemical descriptors and the reported minimum inhibitory concentration values of different derivatives on mycobacterium tuberculosis were used as independent variables and dependent variables respectively. Antituberculosis activity was predicted through QSAR model, developed by forward feed multiple linear regression method with leave-one-out approach. Relationship correlating measure of QSAR model was 85% (R2 =0.85).QSAR studies indicate that Principal moment of inertia and log p value correlate with anti-tubercular activity in the case of mannich bases and refractivity and ovality correlate with the anti-tubercular activity of schiff’s bases. These results could offer useful references for understanding mechanisms and directing the molecular design of new lead compounds with improved antitubercular activity. The generated QSAR model revealed the importance of structural, thermodynamic and electro topological parameters. The quantitative structure activity relationship provides an important structural insight in designing of potent antitubercular agents.