For exoskeletons to be successful in real-world settings, they will need to be effective across a variety of terrains, including on inclines. While some single-joint exoskeletons have assisted incline walking, recent successes in level-ground assistance suggest that greater improvements may be possible by optimizing assistance of the whole leg. To understand how exoskeleton assistance should change with incline, we used human-in-the-loop optimization to find whole-leg exoskeleton assistance torques that minimized metabolic cost on a range of grades. We optimized assistance for three expert, able-bodied participants on 5 degree, 10 degree and 15 degree inclines using a hip-knee-ankle exoskeleton emulator. For all assisted conditions, the cost of transport was reduced by at least 50% relative to walking in the device with no assistance, a large improvement to walking that is comparable to the benefits of whole-leg assistance on level-ground. This corresponds to large absolute reductions in metabolic cost, with the most strenuous conditions reduced by 4.9 W/kg, more than twice the entire energy cost of level walking. Optimized extension torque magnitudes and exoskeleton power increased with incline, with hip extension, knee extension and ankle plantarflexion often growing as large as allowed by comfort-based limits. Applied powers on steep inclines were double the powers applied during level-ground walking, indicating that larger exoskeleton power may be optimal in scenarios where biological powers and costs are higher. Future exoskeleton devices can be expected to deliver large improvements in walking performance across a range of inclines, if they have sufficient torque and power capabilities.