High-entropy (HE) materials, renowned for their exceptional chemical and physical properties, have attracted growing interest due to their broad applications across various fields. In this work, we report the synthesis of a compound, (Al0.196Sc0.196In0.196Yb0.196Y0.196)2Mo3O12:0.04Er3+ (HEMO), designed via a high-entropy solid solution strategy based on the A2Mo3O12 framework. The crystal structure, microstructure, elemental valence states, and thermal expansion properties of HEMO were systematically investigated using variable temperature synchrotron X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy. HEMO exhibits negative thermal expansion (NTE) in the temperature range of 300–1000 K due to coupled polyhedral rotations. Under 980 nm excitation, its upconversion luminescence (UCL) shows remarkable negative thermal quenching (NTQ), with a 53.4-fold increase in intensity between 300 and 650 K. Based on the fluorescence intensity ratio technique, it shows a max relative sensitivity (Sr) of 0.84% K−1 (300 K) at 300–650 K. This work not only reports a high-entropy NTE phosphor but also opens an avenue for exploring UCL phosphors with NTQ luminescence.