Research has linked cultural differences between a sojourner’s home and host country with their cultural transformation. Nonetheless, the results of empirical studies are inconclusive due to different operationalizations of cultural differences and testing among different groups of sojourners. We extend previous investigations by examining the effects of cultural novelty (i.e., the subjective perception of cultural differences) on the experience of international students (N = 1114) in Denmark, Germany, Italy, Poland, and the USA. Drawing on acculturation and social learning theories, we conceptualized a model of students’ adjustment and satisfaction taking into account cultural novelty. We tested the model through multi-group structural equation modeling (SEM) and examined the various relationships across subsamples from all five countries. We determined the significant effects of cultural novelty and a range of factors impacting students’ intercultural experience, such as their cultural intelligence, cultural background, second-language skills, time in the host country, and socialization with domestic students, and how the effects may vary by the host country. We discuss implications for future research and practice.