Developing functionalized 3D covalent organic frameworks (3D COFs) is critical to broaden their potential applications. However, the introduction of specific functionality in 3D COFs remains a great challenge because most of the functional groups are not compatible with the synthesis conditions. Herein, for the first time 3D thioether-based COFs (JUC-570 and JUC-571) for mercury (Hg 2+) removal from aqueous solution is reported. These 3D thioether-based COFs prepared by the bottom-up approach display high Hg 2+ uptakes (972 mg g −1 for JUC-570 and 970 mg g −1 for JUC-571 at pH = 5), fast adsorption kinetics (distribution coefficient Kd value of 2.29 × 10 7 mL g −1 for JUC-570 and 2.07 × 10 7 mL g −1 for JUC-571), and favorable selectivity. In particular, JUC-570 is periodically decorated with isopropyl groups around imine bonds that markedly improve its chemical stability and effectively prevent the pore collapse, and thus endows high Hg 2+ adsorption capacity (619 mg g −1) and excellent cycle performance even at pH = 1. This study not only puts forward a new route to construct stable functionalized 3D COFs, but also promotes their potential applications in areas related to the environment.