Existing therapies for toxoplasmosis have numerous deficiencies including frequent toxic side effects and the inability to completely eradicate infection. We have screened the Global Health Chemical Diversity Library (GHCDL) for activity against T. gondii tachyzoites. The GHCDL is a 68,000-member library of diverse molecules selected for physicochemical characteristics that predict excellent oral absorption and widespread distribution into diverse tissues. In this screen, the largest ever conducted against T. gondii, we identified a novel molecule with a 2,3-dihydro-1,4-benzodioxin chemotype that inhibits the growth of T. gondii tachyzoites in vitro with an EC50 of 275 nM. This compound and related derivatives also prevent the regrowth of T. gondii tachyzoites in vitro at concentrations that are a half log (3.16x) above their EC50s. While current drugs in clinical use and compounds in preclinical development can prevent the in vitro regrowth of T. gondii, typically concentrations that are hundreds or thousands of multiples of the EC50 are needed. This finding suggests that the 2,3-dihydro-1,4-benzodioxins interrupt a vital process in T. gondii, one that may allow for a therapy capable of eradicating infection. We present data regarding the structure-activity relationships of the 2,3-dihydro-1,4-benzodioxin chemotype as well as genetic evidence which supports a novel mode of action. Future efforts will focus on creating derivatives with enhanced potency and metabolic stability.