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 non-disabled, expert 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, which is a large improvement to walking comparable to the benefits of whole-leg assistance on level-ground (N = 3). Optimized extension torque magnitudes and exoskeleton power increased with incline. Hip extension, knee extension and ankle plantarflexion often grew as large as allowed by comfort-based limits. Applied powers on steep inclines were double the powers applied during level-ground walking, indicating that greater exoskeleton power may be optimal in scenarios where biological powers and costs are higher. Future exoskeleton devices could deliver large improvements in walking performance across a range of inclines if they have sufficient torque and power capabilities.