Lost circulation, the significant penetration of drilling fluid into formations during drilling, leads to excessive fluid consumption, non-productive time, and potential well control incidents. This study developed a tunable polymer gel system for plugging lost circulation zones of various scales. Its mechanical properties can be controlled by adjusting the concentration, temperature, gelling time, and aging time. At 120 °C and 10 h gelling time, increasing concentration from 12% to 20% steadily enhanced mechanical properties: storage modulus rose from 750 to 3171 Pa, and tensile stress increased from 20.03 to 67.8 kPa. However, under different temperature and time regimes, the mechanical properties of polymer gels first strengthened and then weakened or showed a trend of strengthening, weakening, and then strengthening again. For example, under gelling temperature 120 °C and 14% concentration, when the gelling time was increased from 4 to 10 h, the tensile stress of polymer gel increased from 4.103 to 30.07 kPa, but when the gelling time was further extended from 10 to 12 h, the tensile stress was reduced from 30.07 to 11.33 kPa. With further extension of time to 14 h, the tensile stress increased again to 43.91 kPa. Comprehensive microstructural analysis revealed how these factors influence gel properties. Subsequently, the simulated plugging experiments of fractures and sand-filled pipes were conducted using the polymer gel with a concentration of 14% and a temperature of 140 °C for 8 h, and the plugging strength was 5.8 MPa for the parallel fracture of 5 mm, and 10.06 MPa for the sand-filled pipe with a 3 mm fracture and an inner diameter of 3 cm in the outlet pipe, which indicated that the polymer gel system exhibited strong pressure-bearing plugging ability for both the fracture and the fracture/vuggy. The proposed polymer gel was applied in the field of HD29-H8 well in the Tarim Basin of Xinjiang, China, and successfully plugged the loss formation above 5000 m, which demonstrated that it can effectively plug high-temperature and high-pressure reservoirs.