Regional, multi-actor environmental collaborations bring together diverse parties to achieve environmental protection and stewardship outcomes. Involving a range of participants helps involve alternative forms of knowledge, expertise, and perspectives; it may also present greater challenges in reaching agreements, particularly when both Indigenous and non-Indigenous parties are involved. The authors conduct a cross-case study of 39 regional partnerships involving Indigenous nations from the Great Lakes basin of North America with the aim of determining the factors that enable Indigenous partners to remain engaged in multi-actor collaborations. Six characteristics influenced Indigenous nations’ willingness to remain engaged: respect for Indigenous knowledges, control of knowledge mobilization, intergenerational involvement, self-determination, continuous cross-cultural education, and early involvement. Being attentive of these factors can help partnerships achieve their environmental goals by keeping important partners at the table.