The Mississippi River has always facilitated currents of trade, activism, art, and research as a site of constant cultural, environmental, and political exchange. As a collective of graduate students and junior faculty, and as members of the Mellon Foundation Humanities Without Walls (HWW) project, “Indigenous Art and Activism in Changing Climates: The Mississippi Valley, Colonialism, and Climate Change,” we bring together responses to the Open Rivers prompt that foreground collaborative and interdisciplinary approaches and highlight multidimensional understandings of Indigenous relationally with the river and its tributaries. Project participants came from six different institutions and we met as a group at sites from the headwaters of the Mississippi to the Gulf, reading scholarly and creative texts about these places while prioritizing embodied, experiential research methods—from canoeing, to visiting Indigenous earthworks, and hearing from and working with Indigenous artists and community members. Over two years of gathering along the river and researching, we have generated individual and collective questions about the Mississippi that connect Indigenous engagements with the river to thinking through decolonizing methodologies and global environmental challenges: What confluences have emerged between Indigenous research, art, and activism in the context of the river? What does “humanities without walls” mean in the context of Indigenous Studies? How are particular Indigenous river histories made visible by collaborative practices and pedagogies of art and activism? As part of our emphasis on team-based research, our responses to these questions regarding environmental stewardship, place, and community are developed in conversation with each other and, much like a river’s tributaries, take shared waters in different directions.