Gaizauskaite et al. report cryo-EM structures of the Cas9–Cas1–Cas2–Csn2 supercomplex from the Streptococcus thermophilus type II-A CRISPR-Cas system in PAM search and PAM-bound configurations, which provide the structural basis for the functional coupling between Cas9 and the spacer integration machinery, and reveal the multifaceted role of the accessory protein Csn2.