Sexual satisfaction can be important for overall well-being and has been described as a sexual right. Individual and cultural factors, such as gender identity and sexual orientation, may influence the ways in which individuals describe, share, or experience their sexuality. The aims of the present study were to examine the factor structure of the five-item Global Measure of Sexual Satisfaction (GMSEX) in a large sample of adults in relationships, to conduct measurement invariance tests to examine whether the GMSEX functions similarly across language-, country-, gender- and sexual orientation-based subgroups, and to evaluate its validity with sexuality and relationship-related outcomes. Results of a confirmatory analysis among 51,778 participants from 42 different countries across five continents (Mage = 32.39 years, SD = 12.52, 56.9% cisgender women) corroborated the proposed one-dimensional factor structure of the scale. Measurement invariance tests also indicated that the scale was fully invariant across gender- and sexual orientation-based subgroups, and partially invariant across language- and country-based subgroups. The GMSEX correlated negatively with masturbation frequency and relationship length and positively with the frequency of sexual activity. Our findings support the validity of the GMSEX as a short and reliable scale to measure sexual satisfaction across diverse samples.