Electrochemical technology is a robust approach to removing toxic and persistent chlorinated organic pollutants from water; however, it remains a challenge to design electrocatalysts with high activity and selectivity as elaborately as natural reductive dehalogenases. Here we report the design of high-performance electrocatalysts toward water dechlorination by mimicking the binding pocket configuration and catalytic center of reductive dehalogenases. Specifically, our designed electrocatalyst is an assembled heterostructure by sandwiching a molecular catalyst into the interlayers of two-dimensional graphene oxide. The electrocatalyst exhibits excellent dechlorination performance, which enhances reduction of intermediate dichloroacetic acid by 7.8 folds against that without sandwich configuration and can selectively generate monochloro-groups from trichloro-groups. Molecular simulations suggest that the sandwiched inner space plays an essential role in tuning solvation shell, altering protonation state and facilitating carbon−chlorine bond cleavage. This work demonstrates the concept of mimicking natural reductive dehalogenases toward the sustainable treatment of organohalogen-contaminated water and wastewater.