Farnesyltransferase (FTase) catalyses the farnesylation of Ras p21 protein at the cysteine residue of its carboxylterminal CAAX motif, a post-translational modification essential for Ras association with plasma membranes and oncogenic activity. Thus, FTase inhibition represents a potential therapeutic target for anticancer agents. Previously reported natural product FTase inhibitors include manumycin, andrastin D, clavaric acid, and kampanol B. In this study, microbial product screening led to the isolation of new FTase inhibitors—UCF116-A (1), -B (2), and -C (3)—produced by Streptomyces sp. The producing strain was cultivated, and the metabolites were isolated via Diaion HP-20 resin extraction, silica gel column chromatography, and preparative HPLC. Physicochemical characterization revealed molecular formulas of C37H48N2O8, C36H48N2O8, and C34H46N2O8 for 1, 2, and 3, respectively. Structural analysis showed 1-3 are structurally related to the known compound mycotrienin II (4): 1 contains a p-quinone moiety, while 2 and 3 have p-hydroquinone moieties, with differences in their C-11 side chains. FTase inhibition assays demonstrated that 1 and 2 inhibited bovine brain FTase with IC50 values of 1.2 μM and 0.6 μM, respectively, whereas 3 and 4 were inactive at concentrations up to 100 μM. Additionally, 1 and 2 selectively inhibited FTase over geranylgeranyltransferase-I (GGTase-I). Kinetic analysis revealed that 2 acts as a competitive inhibitor with the Ras protein substrate, with an apparent Ki of 5.9 μM. UCF116 compounds represent a new class of Ras-competitive non-CAAX mimetic FTase inhibitors, where the C-11 substituent and the cyclohexenecarboxylalanine moiety of 2 are critical for FTase inhibitory activity.