A series of novel coumarin-furoquinoline conjugates were designed, synthesized and screened for antitubercular activity against two mycobacterial strains (Mycobacterium tuberculosis H37 RV and Mycobacterium phlei). The preliminary bioassay results demonstrated that all tested compounds exhibited the activities with different degrees, and some compounds showed better effects than standard drugs used. The SAR results indicate that the compounds bearing hydroxyl group (8g), chlorine (8h, 8i, 9h, 9i, 10h, 10i) and bromine (8j, 9j, 10j) on coumarin and chlorine on furoquinoline are most effective. Further, molecular docking studies performed on all the title compounds, compound 8g and 10h resulted as potent. This is the first report assigning in vitro anti-mycobacterial and structure activity relationship with molecular docking studies on this new class of conjugates.