The Paris Agreement and SDG13 on Climate Action require a global drop in 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. Here we describe 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. We highlight critical R&I actions in cities, based on three pillars: (1) innovative technology and integration (2) governance innovation and (3) social innovation. Further, we stress the research needs to harmonize climate mitigation and adaptation in cities.