The ubiquitin ligase CHIP plays an important role in cytosolic protein quality control by ubiquitinating proteins chaperoned by Hsp70/Hsc70 and Hsp90, thereby targeting such substrate proteins for degradation. We present a 2.91 Å resolution structure of the tetratricopeptide repeat (TPR) domain of CHIP in complex with the α-helical lid subdomain and unstructured tail of Hsc70. Surprisingly, the CHIP-TPR interacts with determinants within both the Hsc70-lid subdomain and the C-terminal PTIEEVD motif of the tail, exhibiting an atypical mode of interaction between chaperones and TPR domains. We demonstrate that the interaction between CHIP and the Hsc70-lid subdomain is required for proper ubiquitination of Hsp70/Hsc70 or Hsp70/Hsc70-bound substrate proteins. Posttranslational modifications of the Hsc70 lid and tail disrupt key contacts with the CHIP-TPR and may regulate CHIP-mediated ubiquitination. Our study shows how CHIP docks onto Hsp70/Hsc70 and defines a bipartite mode of interaction between TPR domains and their binding partners. Display omitted •Hsc70/Hsp70 engage in novel bipartite binding mode with CHIP•Hsp70-lid interaction with CHIP is required for ubiquitination of Hsp70 clients•TPR:lid-tail structure allows modeling of full-length Hsp70:CHIP complexes•Phosphorylation or methylation of Hsp70-lid residues regulate interaction with CHIP Zhang et al. report a novel interaction between Hsp70 and CHIP. This interaction allows for full-length models of the CHIP/Hsp70 complex to be assembled, predicts how Hsp70 posttranslational modifications regulate ubiquitination, and suggests a new mode of chaperone/cochaperone interactions.