Among the most prevalent natural hazards, flooding has been threatening human lives and properties. Robust flood simulation is required for effective response and prevention. Machine learning is widely used in flood modeling due to its high performance and scalability. Nonetheless, data pre-processing of heterogeneous sources can be cumbersome, and traditional data processing and modeling have been limited to a single resolution. This study employed an Icosahedral Snyder Equal Area Aperture 3 Hexagonal Discrete Global Grid System (ISEA3H DGGS) as a scalable, standard spatial framework for computation, integration, and analysis of multi-source geospatial data. We managed to incorporate external machine learning algorithms with a DGGS-based data framework, and project future flood risks under multiple climate change scenarios for southern New Brunswick, Canada. A total of 32 explanatory factors including topographical, hydrological, geomorphic, meteorological, and anthropogenic were investigated. Results showed that low elevation and proximity to permanent waterbodies were primary factors of flooding events, and rising spring temperatures can increase flood risk. Flooding extent was predicted to occupy 135–203% of the 2019 flood area, one of the most recent major flooding events, by the year 2100. Our results assisted in understanding the potential impact of climate change on flood risk, and indicated the feasibility of DGGS as the standard data fabric for heterogeneous data integration and incorporated in multi-scale data mining.