Based on intensive and long-term field research and document reviews, this article compares the historic evolution of lithium mining in Chile and Argentina. We highlight national development discourses and government regulatory frameworks in both countries. We illustrate and assess the diverse perceptions and strategies of local actors. Finally, we discuss the socio-spatial materialization of lithium mining in terms of power relations, ecology, and economy. Using perspectives from political ecology brings to light different power relations between the state, mining companies, and indigenous communities in Chile and Argentina These power asymmetries have an enduring influence on local actors' possibilities for taking action.