<p>Sewage sludge, an unavoidable by-product of biological sewage treatment processes, is a growing environmental burden. If handled properly, it can also be a crucial secondary resource, as it contains many functional microbiomes and useful nutrients. Here we propose an in situ nitrate-driven oxidation approach to upcycle sewage sludge into valuable (&gt;US$4,000 m⁻³) anaerobic ammonium oxidation (anammox) seeds, which are a key ingredient to achieve a fast start-up of the anammox process—a low-carbon nitrogen removal process—in biological sewage treatment facilities. The approach can effectively upcycle sewage sludge rich in endogenous reductants, such as organics and sulfur-based compounds, but poor in oxidative substances. Specifically, this approach employs nitrate-containing wastewater as an oxidant source and utilizes nitrate to oxidize reductants in sewage sludge to provide nitrite for anammox bacterial growth. This approach can initiate anammox seeds within 45 days and form anammox seeds with biomarkers within 90 days. This work reveals the potential of sewage sludge as a source of functional microbiomes and opens a new avenue to sustainable sewage management.</p>