This study presents the development of second spine, an upper body assistive device for human load carriage. The motivation comes from reducing musculoskeletal injuries caused by carrying a heavy load on the upper body. Our aim was to design a wearable upper body device that can prevent musculoskeletal injuries during human load carriage by providing a secondary load pathway—second spine—to transfer the loads from shoulders to pelvis while also allowing a good range of torso motion to the wearer. Static analysis of the backpack and the second spine was first performed to investigate the feasibility of our concept design. The development of second spine had two considerations: load distribution between shoulders and pelvis, and preserving the range of torso motion. The design was realized using load bearing columns between the shoulder support and hip belt, comprising multiple segments interconnected by cone-shaped joints. The performance of second spine was evaluated through experimental study, and its biomechanical effects on human loaded walking were also assessed. Based on the findings from second spine evaluation, we proposed the design of a motorized second spine which aims to compensate the inertia force of a backpack induced by human walking through active load modulation. This was achieved by real-time sensing of human motion and actuating the motors in a way that the backpack motion is kept nearly inertially fixed. Simulation study was carried out to determine the proper actuation of motors in response to the human walking kinematics. The performance of motorized second spine was evaluated through an instrumented test-bed using Instron machine. Results showed a good agreement with simulation. It was shown that the backpack motion can be made nearly stationary with respect to the ground which can further enhance the effectiveness of the device in assisting human load carriage.