This paper proposes a system utilizing a Renishaw XL80 positioning error measuring interferometer and sensitivity analysis design to measure six-degree-of-freedom (6 DOF) geometric errors of a machine tool’s linear guide. Each error is characterized by high independence with significantly reduced crosstalk, and error calculations are extremely fast and accurate. Initially, the real light path was simulated using Zemax. Then, Matlab’s skew ray tracing method was used to perform mathematical modeling and ray matching. Each error’s sensitivity to the sensor was then analyzed, and curve fitting was used to simplify and speed up the mathematical model computations. Finally, Solidworks was used to design the set of system modules, bringing the proposed system closer to a product. This system measured actual 6 DOF geometric errors of a machine tool’s linear guide, and a comparison is made with the Renishaw XL-80 interferometer measurements. The resulting pitch, yaw, horizontal straightness, and vertical straightness error deviation ranges are ±0.5 arcsec, ±3.6 arcsec, ±2.1 μm, and ±2.3 μm, respectively. The maximum repeatability deviations for the measured guide’s pitch, yaw, roll, horizontal straightness, vertical straightness, and positioning errors are 0.4 arcsec, 0.2 arcsec, 4.2 arcsec, 1.5 μm, 0.3 μm, and 3 μm, respectively.