Set-off is the unintentional transfer of substances used in printing from the external printed surface of food packaging to the inner, food-contact surface. Ambient ionization–accurate mass spectrometry (AMI-AMS) detected and identified compounds from print set-off not visible to the human eye. AMI mass spectra from inner and outer surfaces of printed and nonprinted food packaging were compared to detect and identify nonvisible set-off components. A protocol to identify unknowns was developed using a custom open-source database of printing inks and food-packaging compounds. The protocol matched print-related food-contact surface ions with the molecular formulas of common ions, isotopes, and fragments of compounds from the database. AMI-AMS was able to detect print set-off and identify seven different compounds. Set-off on the packaging samples was confirmed using gas chromatographic–mass spectrometric (GC-MS) analysis of single-sided solvent extracts. N-Ethyl-2(and 4)-methylbenzenesulfonamide, 2,4-diphenyl-4-methyl-1(and 2)-pentene, and 2,4,7,9-tetramethyl-5-decyne-4,7-diol were present on the food-contact layer at concentrations from 0.21 to 2.7 ± 1.6 ?g dm–2, corresponding to nearly milligram per kilogram concentrations in the packaged food. Other minor set-off compounds were detected only by AMI-AMS, a fast, simple, and thorough technique to detect and identify set-off in food packaging.