The Nucleosome Remodeling and Deacetylase (NuRD) complex is a multi-protein chromatin-modifying assembly expressed in most tissues and conserved across multi-cellular plants and animals. It regulates gene expression and DNA damage repair by modulating nucleosome accessibility in enhancers and promoters for transcription factors and RNA polymerases. NuRD comprises two catalytic modules – a histone deacetylase module and ATP-dependent chromatin-remodeling module. Despite its importance, limited structural information is available on the complex. We investigated the molecular architecture of three NuRD sub-complexes: MTA1-HDAC1-RBBP4 (MHR), MTA1N-HDAC1-MBD3GATAD2CC (MHM), and MTA1-HDAC1-RBBP4-MBD3-GATAD2 (NuDe) using Bayesian integrative structure determination with IMP (Integrative Modeling Platform), drawing on information from SEC-MALLS, DIA-MS, XLMS, negative stain EM, X-ray crystallography, NMR spectroscopy, and secondary structure and homology predictions. The structures were corroborated by independent cryo-EM maps, biochemical assays, and known cancer-associated mutations. Our integrative structure sheds light on the mechanism by which asymmetry is introduced in NuRD. Our models indicate three previously unrecognized protein-protein interfaces: HDAC1C-MTA1BAH, and HDAC160-100-MBD3, which are being experimentally validated. A significant number of cancer-associated mutations mapped to protein-protein interfaces in our models, including several to the newly described interfaces. Our approach also allows us to localize regions of unknown structure, such as IDRs, thereby resulting in the most complete structural characterization of these NuRD sub-complexes so far.