The great mass extinctions of the fossil record were a major creative force that provided entirely new kinds of opportunities for the subsequent explosive evolution and diversification of surviving clades. Today, the synergistic effects of human impacts are laying the groundwork for a comparably great Anthropocene mass extinction in the oceans with unknown ecological and evolutionary consequences. Synergistic effects of habitat destruction, overfishing, introduced species, warming, acidification, toxins, and massive runoff of nutrients are transforming once complex ecosystems like coral reefs and kelp forests into monotonous level bottoms, transforming clear and productive coastal seas into anoxic dead zones, and transforming complex food webs topped by big animals into simplified, microbially dominated ecosystems with boom and bust cycles of toxic dinoflagellate blooms, jellyfish, and disease. Rates of change are increasingly fast and nonlinear with sudden phase shifts to novel alternative community states. We can only guess at the kinds of organisms that will benefit from this mayhem that is radically altering the selective seascape far beyond the consequences of fishing or warming alone. The prospects are especially bleak for animals and plants compared with metabolically flexible microbes and algae. Halting and ultimately reversing these trends will require rapid and fundamental changes in fisheries, agricultural practice, and the emissions of greenhouse gases on a global scale.