The present study evaluated the anticancer effect of methanolic extract of Cordiadichotoma bark (MECD) against Ehrlich ascites carcinoma (EAC) cells induced in albino mice and against human cancer cell lines (MDA-MB-231 and MCF-7 cells). There were significant fall in the red blood cells (RBC) count and hemoglobin (Hb) content, and significant increase in white blood cells (WBC) count in the EAC control mice as compared to normal control mice. Treatment with MECD (500 mg/kg, b.w., p.o.) or 5-Fluorouracil (20 mg/kg b.w., i.p.) in EAC-cell bearing mice caused a significant (p < 0.01) increase in Hb levels while a significant (p < 0.01) decrease in WBC levels compared to EAC control rats. Also, increase in concentration of MECD dose dependently increased the percent cytotoxicity and decreased the cell viability in both cell line types. The results with MECD were comparable to the tamoxifen. The maximum gain of body weight was observed in the EAC control group. In case of MECD and 5-Fluorouracil treated groups the body weight was significantly (p < 0.01) reduced. The tumor volume and tumor weight were found to be significantly (p < 0.05 or p < 0.01) decreased in MECD treated animals at the doses 250 and 500 mg/kg and 5-Fluorouracil (20 mg/kg) when compared with EAC control animals. With MECD treatment, the survival of EAC bearing mice significantly (p < 0.01) increased as compared to EAC bearing control group. In treated group mean survival time (MST) was significantly increased to 29.0 ± 1.98 (%ILS = 69.04), 34.12 ± 1.84 (%ILS = 81.25), and 36.87 ± 1.67 (%ILS = 87.79), respectively when compared to EAC control group. The results of the current study propose that the antitumor activity of MECD can be inferred from the increased life span of EAC bearing mice which is due to its antioxidant activity.