O-ring sealing systems are ubiquitous in oil/gas field applications and have been extensively tested. The general relationships between O-ring designs and their performances are well known; however, O-ring extrusion failure is still frequently encountered in various applications. As a result, there is still a need to test standard O-rings when changes in materials, sealing gland configuration, or service temperatures occur. This study is intended to uncover universal relationships between O-ring design parameters and their extrusion-resistance performance. A comprehensive experimental program was developed to study the extrusion-resistance performance of four different ISO3601-1 sized O-rings made from a single batch of rubber. The study was conducted at 400°F when subjected to three extrusion gaps, at squeezes of 4%, 10%, and 15%. A total of 160 tests were performed in which the pressures required to extrude the O-rings were measured. The conventional data analysis of the specimens and test results confirmed and quantified well-known trends. Two observations worth noting are that for the same extrusion gaps, smaller-sized O-rings have lower pressures to extrude, and the extrusion pressure at failure is insensitive to squeeze. The dimensional-analysis-based advanced data analytics revealed that the extrusion pressure normalized by material stiffness is uniquely related to a relative extrusion gap. A master curve of normalized extrusion pressure to the relative extrusion gap is established, collapsing curves from test results of all four O-ring sizes into a single curve. This master curve can be used to reduce physical tests for the evaluation of O-ring performance under HPHT conditions.