A model was developed to assess the impact of adding acids and bases to processed municipal sewage sludge (MSS) to mobilize contaminants, facilitating their removal from sludge by flushing prior to land application. Among 312 organic contaminants documented to occur in U.S. MSS, 71 or 23% were identified as ionizable organic contaminants (IOCs), contributing a disproportionately large fraction of 82% of the total mass of sludge-borne contaminants. Detected IOCs included 57 pharmaceuticals and personal care products, 12 perfluorinated compounds, one surfactant and one pesticide. Annually, about 2,000 t of IOCs were estimated to be released to U.S. soils via land-application of MSS. A partitioning model developed to assess the impact of pH on hydrophobic sorption revealed that between 36 and 85% of the mass of individual classes of IOCs potentially could be desorbed from MSS via pH adjustment and flushing. Thus, modeling results suggest that a sequential pH treatment [acidic (~pH 2) followed by basic (~pH 12) treatment] has the potential to reduce the burden of harmful IOCs in MSS applied on U.S. land by up to 40 ± 16 t annually. This approach may serve as a cost-effective treatment process that can be implemented easily in existing sludge treatment infrastructure in the U.S. and worldwide, serving to significantly improve the quality of MSS destined for land application.