A small amount of defocus is generated in the optical system of high-resolution space cameras owing to the harsh mechanical environment of the launch section and the complex temperature environment of the orbit. To ensure the image quality of the camera and correct the defocus, a new high-precision focusing mechanism, consisting of a worm gear and a cam slider, was designed. The first stage of deceleration was achieved through the worm gear in this design. The drive's rotary axis was orthogonal to the optical axis, hence, the mechanism was more compact. Further deceleration was performed by the cam slider mechanism, and the rotary motion was converted into a linear motion; the linear motion accuracy of the slider was provided by a linear guide. The mechanism is small, has high precision, and is capable of self-locking in the case of a power failure. The mechanism motion pair was coated with a solid lubricant to prevent vacuum cold welding. According to the characteristics of the mechanism, the resolution and error of the focusing mechanism were analyzed. Mechanical and thermal vacuum cycle tests were carried out on the mechanism. Various precision indicators of the mechanism were compared and tested before and after the experiments. The results show that the mechanism performance is normal after the environmental test, the focus shift error is better than 5.8 μm, the linearity is better than 0.3%, and the yaw angle is better than 14″. In the thermo-optical test, the focal plane was adjusted by the focusing mechanism, and the image quality was significantly improved. The focusing mechanism can meet the accuracy and environmental adaptability requirements of the optical system.