Weed control is a basic agricultural practice, typically achieved through herbicides and mechanical weeders. Because of the negative environmental impacts of these tools, alternative solutions are being developed and adopted worldwide. Following recent technical developments, an autonomous laser-based weeding system (ALWS) now offers a possible solution for sustainable weed control. However, beyond recent proof of performance, little is known about the adoption potential of such a system. This study assesses the adoption potential of ALWS, using a mixed-method approach. First, six macro-environmental factors regarding the adoption of ALWS were determined. This assessment is referred to as a Political, Economic, Social, Technological, Legal, Environmental (PESTLE) analysis and is conducted in a form of a literature review initiated by expert consultations. Second, a range of European stakeholders’ perceptions of ALWS was evaluated in four focus-group discussions (n = 55), using a strengths, weaknesses, opportunities, threats (SWOT) analysis. The factors identified in the PESTLE and SWOT analyses were subsequently merged to provide a comprehensive overview of the adoption potential of ALWS. Labour reduction, precision treatment and environmental sustainability were found to be the most important advantages of ALWS. High costs and performance uncertainty were identified as the main weaknesses. To promote the adoption of ALWS, this study recommends the following: (1) Concrete performance results, both technical and economic, should be communicated to farmers. (2) Farmers’ knowledge of precision agriculture should be improved. (3) Advantage should be taken of policies that are favourable towards non-chemical methods and the high demand for organic products. This article also extensively discusses regulatory barriers, the risks posed to the safety of both humans and the machines involved, technological challenges and requirements, and policy recommendations related to ALWS adoption.