The Paris Agreement and SDG13 on Climate Action require a global drop in Green House Gases (GHG) emissions to stay within a “well below 2 degrees” climate change trajectory. Cities will play a key role in achieving this, being responsible for 60 to 80% of the global GHG emissions depending on the estimate. This paper describes how Research and Innovation (R&I) can play a key role in decarbonizing European cities, and the role that research and education institutions can play in that regard. The paper highlights critical R&I actions in cities based on three pillars: (1) innovative technology and integration, (2) governance innovation, and (3) social innovation. Further, the research needed to harmonize climate mitigation and adaptation in cities are investigated.