SARS-CoV-2 pandemic has caused more than 676 million cases in the global human population with approximately 7 million deaths and vaccination has been proved as the most effective countermeasure in reducing clinical complications and deaths of SARS-CoV-2 infection. However, the protective elements induced by vaccine are still not completely understood. Various antibodies with multiple protective mechanisms can be induced simultaneously by vaccination in vivo, thereby complicating the identification and characterization of each protective components. Recently, an increasing body of observations suggests that antibody-induced Fc-effector functions play a crucial role in combating SARS-CoV-2 infections, including neutralizing antibodies-escaping variants. Here, we review the recent progress in understanding the impact of Fc-effector functions in broadly disarming SARS-CoV-2 infectivity and discuss various efforts in harnessing this conserved antibody function to develop an effective SARS-CoV-2 vaccine that can protect humans against infections by SARS-CoV-2 virus and its variants of concern (VoCs).