A new method to calculate and counterbalance the inertia force of slider-crank mechanisms in high-speed mechanical presses was put forward. By analyzing the kinematic characteristics of a center-located slider-crank mechanism whose crank rotates at a constant angular velocity, the kinematic parameters of the slide, connecting rod and crank were formulated approximately. On the basis of the results above, three inertia forces and the input moment in the mechanism during its idle running were investigated and formulated by dynamic analysis. A verification experiment was performed on a slider-crank mechanism at a high-speed press machine. The forces derived from the established formulas were compared respectively with those obtained by the ADAMS software and the classical method of connecting rod mass substitution. It was experimentally found that the proposed formulas have an improved performance over related earlier techniques. By use of these results, a 1000 kN 1250 rpm four-point high-speed press machine was designed and manufactured. The slide of this press is driven by four sets of slider-crank mechanisms with symmetrical layout and opposite rotation directions to counterbalance the horizontal inertia forces. Four eccentric counterbalance blocks were designed to counterbalance the vertical force after their mass and equivalent eccentric radius were formulated. The high-speed press machine designed by the proposed counterbalance method has worked with satisfactory performance and good dynamic balance for more than four years in practical production.