Einstein-Podolsky-Rosen (EPR) steering demonstrates that two parties share entanglement even if the measurement devices of one party are untrusted. Here, going beyond this bipartite concept, we develop a novel formalism to explore a large class of EPR steering from generic multipartite quantum systems of arbitrarily high dimensionality and degrees of freedom, such as graph states and hyperentangled systems. All of these quantum characteristics of genuine high-order EPR steering can be efficiently certified with few measurement settings in experiments. We faithfully demonstrate for the first time such generality by experimentally showing genuine four-partite EPR steering and applications to universal one-way quantum computing. Our formalism provides a new insight into the intermediate type of genuine multipartite Bell nonlocality and potential applications to quantum information tasks and experiments in the presence of untrusted measurement devices.