The black garlic is produced from the raw garlic by Milliard reaction at high temperature (~60–90°C) and humidity (~70–90%). In this process, the pungent odor and gastrointestinal irritation effects of the raw garlic are reduced. At the same time, unstable compounds such as allicin are converted into stable organosulfur compounds with antioxidant activity. Previous studies have confirmed that black garlic extract has anti-tumor effects and could inhibit the proliferation of various tumor cells, including breast cancer cells MCF-7. However, the mechanisms of the anti-tumor effects remain unclear. In this study, we found that the black garlic extract could inhibit the proliferation, invasion, and metastasis of estrogen receptor-positive breast cancer cells, promote their apoptosis, and inhibit their epithelial-mesenchymal transition. Mechanistically, the black garlic extract reduced the expression of the anti-apoptotic protein MCL-1, which was achieved by modulating the ROS-JNK signaling pathway. In addition, the black garlic extract also decreased the expression of BCL-2 and increased the expression of BAX and BIM. We also found that the black garlic extract, in combination with venetoclax, a BCL-2 inhibitor, synergistically kills the estrogen receptor-positive breast cancer cells. These results suggested that black garlic extract has great therapeutic value and prospects for estrogen receptor-positive breast cancer treatment.