A series of novel 1,3-oxazole sulfonamides were constructed and screened for their potential to inhibit cancer cell growth. These compounds were evaluated against the full NCI-60 human tumor cell lines, with the majority exhibiting promising overall growth inhibitory properties. They displayed high specificity within the panel of leukemia cell lines versus all other lines tested. When examined in the dose-response assay, GI50 values fell within the low micromolar to nanomolar ranges. 1,3-Oxazole sulfonamide <b>16</b> displayed the best average growth inhibition, whereas the 2-chloro-5-methylphenyl and 1-naphthyl substituents on the sulfonamide nitrogen proved to be the most potent leukemia inhibitors with mean GI50 values of 48.8 and 44.7 nM, respectively. In vitro tubulin polymerization experiments revealed that this class of compounds effectively binds to tubulin and induces the depolymerization of microtubules within cells.