Over the course of the eighteenth century, the petites nations of the Lower Mississippi Valley survived enormous political, demographic, and social change. By the 1690s, these petites nations, as the region’s many small Native polities were collectively known, seemed to be on the verge of destruction. The combined forces of the arrival of British and French colonizers in the Southeast, the spread of devastating epidemics, and the escalation of the Indian slave trade threated to shatter their nations and annihilate their peoples. This dissertation compares the diverse experiences of a few of these petites nations—including the Tunicas, Ofogoulas, Biloxis, Koroas, Mugulashas, Bayagoulas, Mobilians, Chitimachas, and Tensas—as they fought to preserve their homelands and protect their peoples. Unlike the more well-known Southeastern Indian nations, these Native groups did not coalesce or confederate into a single larger polity. Rather, these groups developed extensive alliance networks that would allow them to exert sufficient political and military influence to protect their communities while preserving their autonomy as groups of fewer than 1,000 individuals. The relationships the petites nations forged with their black, white, and Indian neighbors fundamentally shaped the geopolitical structure not only of the Native southeast, but also of European settlement in the Lower Mississippi Valley. By demonstrating the importance of Indigenous networks on colonial Louisiana, this dissertation highlights the influence of politics within Indian country on the region as a whole. Ultimately by relying on combinations of strategic mobility and violence, social and economic adaptability, and numerous political relationships with both their Native and European neighbors, many of these nations were able not only to survive this tumultuous era, but also to exert tremendous regional power.