Ecosystem-based management (EBM) in marine ecosystems considers impacts caused by complex interactions between environmental and anthropogenic pressures (i.e., oceanographic, climatic, socio-economic) and marine communities. EBM depends, in part, on ecological indicators that facilitate understanding of inherent properties and the dynamics of pressures within marine communities. Thresholds of ecological indicators delineate ecosystem status because they represent points at which a small increase in one or many pressure variables results in an abrupt change of ecosystem responses. The difficulty in developing appropriate thresholds and reference points for EBM lies in the multidimensionality of both the ecosystem responses and the pressures impacting the ecosystem. Here, we develop thresholds using gradient forest for a suite of ecological indicators in response to multiple pressures that convey ecosystem status for large marine ecosystems from the US Pacific, Atlantic, sub-Arctic, and Gulf of Mexico. We detected these thresholds of ecological indicators based on multiple pressures. Commercial fisheries landings above approximately 2–4.5 t km−2 and fisheries exploitation above 20–40% of the total estimated biomass (of invertebrates and fish) of the ecosystem resulted in a change in the direction of ecosystem structure and functioning in the ecosystems examined. Our comparative findings reveal common trends in ecosystem thresholds along pressure gradients and also indicate that thresholds of ecological indicators are useful tools for comparing the impacts of environmental and anthropogenic pressures across multiple ecosystems. These critical points can be used to inform the development of EBM decision criteria.