Abstract In a future energy system prospective, predictably dominated by (often) remote and (always) unsteady, nondispatchable renewable power generation from solar and wind resources, hydrogen (H2) and ammonia (NH3) have emerged as logistically convenient, chemically simple and carbon-free chemicals for energy transport and storage. Moreover, the reliability of supply of a specific fuel feedstock will remain unpredictable in the upcoming energy transition period. Therefore, the ability of gas turbine combustion systems to seamlessly switch between very disparate types of fuels must be ensured, aiming at intrinsically fuel-flexible combustion systems, i.e., capable of operating cleanly and efficiently with novel carbon-free energy vectors like H2 and NH3 as well as conventional fossil fuels, e.g., natural gas or fuel oils (back-up feedstock). In this context, a convenient feature of Ansaldo's constant pressure sequential combustion (CPSC) system, resulting in a fundamental advantage compared to alternative approaches, is the possibility of controlling the amount of fuel independently fed to the two combustion stages, depending on the fuel reactivity and combustion characteristics. The fuel-staging strategy implemented in the CPSC system, due to the intrinsic characteristics of the auto-ignition stabilized reheat flame, has already been proven able of handling fuels with large hydrogen fractions without significant penalties in efficiency and emissions of pollutants. However, ammonia combustion is governed by widely different thermo-chemical processes compared to hydrogen, requiring a considerably different approach to mitigate crucial issues with extremely low flame reactivity (blow-out) and formation of significant amounts of undesired pollutants and greenhouse gases (NOx and N2O). In this work, we present a fuel-flexible operational concept for the CPSC system and, based on unsteady Reynolds-Averaged Navier–Stokes (uRANS) and large eddy simulation (LES) performed in conjunction with detailed chemical kinetics, we explore for the first time full-load operation of the CPSC architecture in a Rich-Quench-Lean (RQL) strategy applied to combustion of partially-decomposed ammonia. Results from the numerical simulations confirm the main features of ammonia-firing in RQL operation already observed from previous work on different combustion systems and suggests that the CPSC architecture has excellent potential to operate in RQL-mode with low NOx and N2O emissions and good combustion efficiency.