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Quantum electrodynamics (QED), the quantum field theory that describes the interaction between light and matter, is commonly regarded as the best-tested quantum theory in modern physics. However, this claim is mostly based on extremely precise studies performed in the domain of relatively low field strengths and light atoms and ions 1-6 . In the realm of very strong electromagnetic fields such as in the heaviest highly charged ions (with nuclear charge Z ≫ 1), QED calculations enter a qualitatively different, non-perturbative regime. Yet, the corresponding experimental studies are very challenging, and theoretical predictions are only partially tested. Here we present an experiment sensitive to higher-order QED effects and electron-electron interactions in the high-Z regime. This is achieved by using a multi-reference method based on Doppler-tuned X-ray emission from stored relativistic uranium ions with different charge states. The energy of the 1s 1/2 2p 3/2  J = 2 → 1s 1/2 2s 1/2  J = 1 intrashell transition in the heaviest two-electron ion (U 90+ ) is obtained with an accuracy of 37 ppm. Furthermore, a comparison of uranium ions with different numbers of bound electrons enables us to disentangle and to test separately the one-electron higher-order QED effects and the bound electron-electron interaction terms without the uncertainty related to the nuclear radius. Moreover, our experimental result can discriminate between several state-of-the-art theoretical approaches and provides an important benchmark for calculations in the strong-field domain., (© 2024. The Author(s).)