Over 17,000 participants responded to self-report measures of sexuality and personality as part of the International Sexuality Description Project. It was expected that romantic relationship infidelity would be associated with the personality traits of disagreeableness and a lack of conscientiousness across most cultures. Sexual promiscuity, on the other hand, was expected to relate to extraversion across most cultures. Analyses across 58 cultures from 52 nations revealed that romantic relationship infidelity was significantly associated with disagreeableness and low levels of conscientiousness across most cultures. Sexual promiscuity was related to extraversion across many, but not most, cultural regions. The expected pattern of findings was most strongly evident in South America, Western Europe, Eastern Europe, the Middle East, and Oceania. In some world regions, such as Africa and East Asia, sexual promiscuity was completely unrelated to extraversion levels. Discussion questions focus on why regional differences in sexuality-personality linkages seem to exist.