The urgency to achieve carbon neutrality underlines the importance of shifting from carbon‐based fossils to renewable resources. Bio‐based polyethylene (bio‐PE) is a key component of this transition, which is obtained from natural and renewable sources such as sugarcane. The environmental impact of bio‐PE and fossil‐based PE production is compared building ad‐hoc sustainability indicators while exploring environmental, social, economic, and energetic aspects to provide a comprehensive evaluation. This methodology involves analyzing the entire lifecycle of both processes for polyethylene production, from extraction/harvesting to post‐disposal actions, such as mechanical recycling or incineration. The main goal is to represent numerous sustainability indicators on a radar diagram, thus comparing process scores of sustainability. Bio‐PE production has significantly higher scores than fossil carbon PE in terms of global warming potential (from cradle‐to‐gate), safety, and contribution to ozone depletion. Additionally, bio‐PE offers a quite better scenario in terms of mass input and energy operating costs. On one side, bio‐PE exhibits similar potential of eutrophication and acidification; on the other side, it also guarantees almost same potential revenues. This can address the choice to the most sustainable post‐disposal method, that regards the mechanical separation and re‐introduction of end‐of‐life PE into the manufacturing process.