Display omitted •A novel three-stage process, comprising PN/A, acidic PN, and anammox, is proposed.•The PN/A unit requires residual ammonium to suppress nitrite-oxidizing bacteria (NOB).•The acidic PN unit provides stable nitrite sources to the anammox unit.•The anammox unit removes the residual ammonium and nitrite from the PN/A and the acidic PN units.•The overall nitrogen removal efficiency is higher than 90% based on model simulation. Sewage treatment with partial nitritation and anammox (PN/A, also termed as deammonification) has gained widespread attentions over the past decade, driven by the need of establishing energy-neutral/positive sewage treatment plants (STPs). However, a key challenge for the mainstream deammonification is to achieve stable suppression of nitrite-oxidizing bacteria (NOB). Deammonification can be configured in either one reactor or two reactors (where PN and anammox are separated), known as one-stage and two-stage configurations, respectively. This study first analyses the current bottlenecks in one-stage and two-stage deammonification. To address these issues, a new, three-stage configuration is proposed. Three-stage deammonification comprises three components, including a PN/A reactor, an acidic PN reactor, and an anammox reactor. The majority of sewage is allocated to the PN/A reactor, which produces an effluent with an elevated level of residual ammonium (2–40 mg N L−1), as required for NOB suppression in this reactor. The residual ammonium is removed in the anammox reactor, using the nitrite supplied from the acidic PN reactor. The acidic PN reactor is fed with a mixture of sewage and anaerobic digestion liquor with a ratio that allows the attainment of a low pH (<6.0) and NOB suppression. This three-stage process was shown applicable to a wide range of municipal wastewaters which have a HCO3–/ NH4+ mole ratio of 1.17–2.41, based on mass balance. Further, simulation indicates that this three-stage process can deliver a stable and high-quality effluent, with the total nitrogen < 10 mg N L−1 and the nitrogen removal efficiency > 90%.