Elastomeric O-ring seals are widely used in static and dynamic applications. A compressed and highly pressurized O-ring seal inserted under laterally one-sided constrained condition has been analyzed experimentally and numerically. The deformed shape and extrusion length of the O-ring under high pressure has been measured by the computed tomography. Through the comparison of experimental and FE results, the numerical analysis technique has been verified. Using verified FE method, the contact stress profiles at sealing surfaces have been investigated and their relevance to the 0-ring performance evaluated based on stress-related and displacement-related parameters. It has been found that the contact stress profiles and deformation behaviors of the seal are affected by friction coefficient, gap clearance, and pressure considerably.