ABSTRACT Strategies for tackling environmental issues, including the consequences of invasive species and corresponding control efforts, are frequently approached through a Western scientific lens that often overlooks Indigenous rights and Indigenous knowledge systems. This can cause numerous issues from costly delays in implementing control programmes, overlooking vital ecosystem information and alternative options, legal action due to infringement on rights, and perpetuating systems of oppression. This research uses social science and Indigenous methodologies to understand the Denny’s Dam rehabilitation (DDR) as a case study for relationship-building and knowledge coexistence between the Saugeen Ojibway Nation and the Great Lakes Fisheries Commission in controlling sea lamprey (Petromyzon marinus), an invasive species in the Laurentian Great Lakes. To evaluate the successes and shortcomings of the project, virtual semi-structured interviews (n = 14) were conducted with key decision-makers and others involved in the rehabilitation of Denny’s Dam, a sea lamprey barrier. Analysis of these interviews identify four main factors that were crucial in the success of the DDR partnership: meaningful communication, funding and capacity, going beyond duty to consult requirements, and early engagement. The DDR shows how knowledge coexistence approaches, including Two-Eyed Seeing, can lead to equitable decision-making, foster collaboration, and contribute to addressing challenges like climate change, invasive species, and various environmental degradation.