The group of parasites causes Nagana in cattle and human African trypanosomiasis, or sleeping sickness, in humans. Current drugs against these parasites have severe toxicity, vaccines are not available, and development of drug resistance makes finding new chemotherapeutic targets imperative. Ion channels, which are involved in several biological processes, are targets of many therapeutically useful agents, and they remain significantly underexplored as therapeutic targets in parasites. Here, we report the presence of a voltage gated Ca channel (VGCC, TbCa), which is localized in the flagellar plasma membrane (PM) of and is essential for proliferation of both bloodstream (BSF) and procyclic forms (PCF) of the parasite. TbCa is a single subunit channel capable of transporting Ca when expressed in mutant yeast lacking PM Ca channels or in HEK293T cells. Through the virtual screening of a commercial chemical library using dynamic ensembles of various conformations of TbCa and associated docking analyses, several inhibitors of TbCa were discovered. As pharmacological validation of the essential roles of TbCa, these compounds were shown to inhibit growth with the most potent agent, -(7-nitro-2,1,3-benzoxadiazol-4-yl) acetamide (NBD-A), exhibiting an EC of 25 ± 3 nM and no cytotoxicity in Vero cells possessing related channels. Thus, such studies constitute pharmacological validation of TbCa as a viable therapeutic target of .