Structural members carry spatial loads owing to, for example, gravity, winds, and earthquakes. Loads along multiple degrees of freedoms (DOF) should be synchronously imposed on the loading point for accurately reproducing structural responses under spatial loading. Strong coupling may exist among the multiple DOFs owing to specimen rigidity, posing significant challenges for actuator control. Two major problems should be solved to address this challenge. The first is the nonlinear coordinate transformation from the local actuator space (LAS) to the global Cartesian coordinate (GCC) system, depending on the current GCC position of the loading point. The second is the mixed control scheme for engineering specimens, that is, force control in rigid directions and simultaneous displacement control in soft directions, which depends greatly on the nonlinearities developed in specimens. To overcome these difficulties, a modified Newton-Raphson (NR) iteration integrated with a PI control (MNR-PI) is developed to handle material nonlinearity, and the incremental kinematic transformation method integrated with PI control (IKT-PI) is proposed to solve the nonlinear coordinate transformation problem. The theoretical background of the MNR-PI, which can be synchronously incorporated with the control process of the loading system to solve nonlinear problems, is first provided. The control gains are then designed by discrete control theory, and a new MDOF force-displacement mixed control method is accordingly formulated and numerically simulated. Finally, three-DOF cyclic tests on a steel column are conducted to demonstrate the feasibility and accuracy of the proposed method.