Does quantum theory apply at all scales, including that of observers? New light on this fundamental question has recently been shed through a resurgence of interest in the long-standing Wigner’s friend paradox. This is a thought experiment addressing the quantum measurement problem—the difficulty of reconciling the (unitary, deterministic) evolution of isolated systems and the (non-unitary, probabilistic) state update after a measurement. Here, by building on a scenario with two separated but entangled friends introduced by Brukner, we prove that if quantum evolution is controllable on the scale of an observer, then one of ‘No-Superdeterminism’, ‘Locality’ or ‘Absoluteness of Observed Events’—that every observed event exists absolutely, not relatively—must be false. We show that although the violation of Bell-type inequalities in such scenarios is not in general sufficient to demonstrate the contradiction between those three assumptions, new inequalities can be derived, in a theory-independent manner, that are violated by quantum correlations. This is demonstrated in a proof-of-principle experiment where a photon’s path is deemed an observer. We discuss how this new theorem places strictly stronger constraints on physical reality than Bell’s theorem.