Cancer continues to be one of the biggest threats to the human civilization because there is no cure of it. Small heterocyclic molecule with low molecular weight and novel structural feature is therapeutically highly demanding. These molecules have the capability to disrupt signaling pathways leading to anticancer activities. Therefore, the search for new anticancer agents continues to draw attention to the research community. In this study, a small triazolo-benzoxazepine scaffolds was synthesized using a one-pot four-step synthetic methodology involving click reaction. Small libraries of 12 compounds were successfully synthesized and screened them against different cancer cell lines. Low micromolar anticancer activity was recorded using MTT assay, and further confirmation of cell death was obtained by phase contrast, fluorescent, and confocal images.