Kesterite‐based Cu2ZnSn(S,Se)4 semiconductors are emerging as promising materials for low‐cost, environment‐benign, and high‐efficiency thin‐film photovoltaics. However, the current state‐of‐the‐art Cu2ZnSn(S,Se)4 devices suffer from cation‐disordering defects and defect clusters, which generally result in severe potential fluctuation, low minority carrier lifetime, and ultimately unsatisfactory performance. Herein, critical growth conditions are reported for obtaining high‐quality Cu2ZnSnSe4 absorber layers with the formation of detrimental intrinsic defects largely suppressed. By controlling the oxidation states of cations and modifying the local chemical composition, the local chemical environment is essentially modified during the synthesis of kesterite phase, thereby effectively suppressing detrimental intrinsic defects and activating desirable shallow acceptor Cu vacancies. Consequently, a confirmed 12.5% efficiency is demonstrated with a high VOC of 491 mV, which is the new record efficiency of pure‐selenide Cu2ZnSnSe4 cells with lowest VOC deficit in the kesterite family by Eg/q‐Voc. These encouraging results demonstrate an essential route to overcome the long‐standing challenge of defect control in kesterite semiconductors, which may also be generally applicable to other multinary compound semiconductors. Kesterite Cu2ZnSnSe4 (CZTSe) thin‐film solar cells with independently confirmed 12.5% total area efficiency are demonstrated using a novel strategy to effectively control the formation of intrinsic defects and defect clusters in CZTSe by carefully engineering the local chemical environment (e.g., suitable local chemical composition, oxidation states of cations) during film growth.