Forward osmosis (FO) is an emerging technology for wastewater treatment and reclamation. However, membrane fouling remains a strong hindrance to FO application. We proposed a novel approach for alleviating FO membrane fouling via in situ removing Ca2+ binding with organic foulants using the EDTA-based adsorption layer. Results suggested that the EDTA-based adsorption layer can effectively remove the Ca2+ binding with sodium alginate, and its adsorption capacity correspondingly increased as a function of Ca2+ concentration in the feed solution. Owing to the effective extraction of Ca2+ from the fouling layer by the EDTA-based adsorption layer, water flux of FO membrane was significantly enhanced, and fouling layer became easily removed by physical flushing, suggesting a remarkable alleviation of FO membrane fouling. Mitigation of FO membrane fouling by the EDTA-based adsorption layer was attributed to the fact that the fouling layer structure became more porous and looser after in situ removing Ca2+ from the alginate-Ca2+ gel networks. This study demonstrated a novel fouling control strategy via in situ removing Ca2+ binding with the organic foulants, providing a new avenue for FO membrane fouling management.