We use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ∼10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs “facing” one another. The inactive X chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats. Display omitted Display omitted •Contact domains (∼185 kb) segregate into six subcompartments with distinct histone marks•Loop anchors occur at domain boundaries and bind CTCF in a convergent orientation•Loops correlate with gene activation and are conserved across cell types and species•The inactive X chromosome contains large loops anchored at CTCF-binding repeats Using 3D genome sequencing, we find ∼10,000 DNA loops across the human genome. Loop anchors typically occur at domain boundaries and bind CTCF in a convergent orientation, with the asymmetric motifs “facing” one another. On the inactive X chromosome, large loops are anchored at CTCF-binding repeats. Loops are conserved across cell types and species.