The synthetic macrocycle cucurbit[6]uril forms host-guest inclusion complexes with molecular dibromine and diiodine. As evidenced by their crystal structures, the encapsulated dihalogens adapt a tilted axial geometry and are held in place by two different types of halogen-bonding interactions, one with a water molecule (bond distances 2.83 angstrom for O center dot center dot center dot Br and 3.10 angstrom for O center dot center dot center dot I) and the other one with the ureido carbonyl groups of the molecular container itself (bond distances 3.33 angstrom for O center dot center dot center dot Br and 3.49 angstrom for O center dot center dot center dot I). While the former is of the conventional type, involving the lone electron pair of an oxygen donor, the latter is perpendicular, involving the pi-system of the carbonyl oxygen (N-C=O center dot center dot center dot X dihedrals ca. 90 degrees). Such perpendicular interactions resemble those observed in protein complexes of halogenated ligands. A statistical analysis of small-molecule crystal structural data, as well as quantum-chemical calculations with urea as a model (MP2/aug-cc-pVDZ-PP), demonstrates that halogen bonding with the pi-system of the carbonyl oxygen can become competitive with the commonly favored lone-pair interaction whenever the carbonyl group carries electron-donating substitutents, specifically for ureas, amides, and esters, and particularly when the lone pairs are engaged in orthogonal hydrogen bonding (hX bonds). The calculations further demonstrate that the perpendicular interactions remain significantly attractive also for nonlinear distortions of the O center dot center dot center dot X-X angle to ca. 140 degrees, the angle observed in the two reported crystal structures. The structural and theoretical data jointly support the assignment of the observed dihalogen-carbonyl contacts as genuine halogen bonds.