The vast territorial expanse and unique geographical position of Sasanian Iran necessitated that major inter-civilizational trade and communication routes between East and West either traverse the Sasanian heartland or skirt its peripheries. This strategic geography played a pivotal role in advancing the Sasanian policy of expansionism and economic monopolization, as well as in facilitating commercial, cultural, and political interactions with regional and trans-regional polities. Within this context, examining the political-cultural relations between the Sasanians and ancient Yemen is of particular significance, given both territories’ possession of maritime fronts and their associated trade networks. Consequently, this research aims to investigate the nature and depth of the political and cultural relations between the Sasanians and Yemen, to identify the factors influencing the formation and evolution of these relations, and to assess the reciprocal impact of these relations on the historical developments of both lands. Furthermore, the role of archaeology in elucidating various dimensions of these relations will be considered. Through an analysis of historical and archaeological evidence, this study seeks to answer the following question: What factors led to the formation and perpetuation of political and cultural relations between the Sasanians and Yemen from the 4th to the 7th centuries CE? The findings indicate that hegemony over maritime trade routes played a central role in the interactions between Iran and Yemen during the Sasanian period. Moreover, the results of an examination of the artistic characteristics of specific archaeological finds from Yemen—namely, the Knight relief (from Dhofar), a female figure relief (from Dhofar), a fragment of a decorated textile depicting a Sasanian battle scene with Ethiopians (from Antinoë), and a carved four-faced capital (from the Qalʿa of Ḥasan al-ʿUr in Yemen)—reveal shared features with Sasanian art and corroborate the cultural-artistic influence of the Sasanians in the land of Yemen.