Multiple clamps are frequently used to serve the purpose of workholding in a fixture. So multiple clamping forces including their magnitudes, placements and application sequences, greatly influence contact forces and workpiece machining accuracy. In this paper, the impact of multiple clamping forces on workpiece location error is formulated analytically for a workpiece-fixture system. The proposed model takes into account the varying contact forces and friction force during entire clamping operation. It reveals that the historical accumulation of clamping steps influences heavily the final distribution of contact forces in the workpiece-fixture system. In addition, based on effect of contact forces from one step to another on workpiece location, a novel design model is presented to optimize the multiple clamping forces in order to minimize the workpiece location errors. Some numerical tests are finally demonstrated to validate the proposed model and approach.