For the trans-scale three-dimensional (3D) measurement in regular-size space and industrial applications, there are many deficiencies and application limitations for traditional measurement methods. Reference to the three axes architecture of traditional instruments, a novel non-orthogonal shafting laser sensor is proposed. The novel sensor is mainly composed of two non-orthogonal shafting laser sensing modules, and each module is made up of two one-dimensional rotary tables and one collimated laser. In the novel laser sensing module, the three axes represent a non-orthogonal shafting architecture, with no orthogonal and intersecting requirements. The manufacturing and application costs are greatly reduced. A high-accuracy calibration method based on coordinate measuring machine and image processing is introduced. An improved perspective projection transform model and attitude kinetic model described by quaternion are adopted to calculate the 3D coordinates of spatial points. The simulation and experimental results showed that a maximum error less than 0.1 mm was detected from 100 mm to 500 mm. It is proved that trans-scale 3D measurement is feasible with the proposed non-orthogonal shafting laser sensor.