Cooked, milled purple-fleshed sweet potato (PFSP) accessions, PM09.812 and PM09.960, underwent digestion in a dynamic human gastrointestinal (GI) model that simulates gut digestive conditions to study the bioaccessibility and biotransformation of anthocyanins. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry showed accession-dependent variations in anthocyanin release and degradation. After 24 h, more anthocyanin species were detected in the small intestinal vessel relative to other vessels for accession PM09.960 whereas more species appeared in the ascending colonic vessel for accession PM09.812. The ferric reducing antioxidant power was increased in the small intestinal vessel for PM09.960 and in the ascending colonic vessel for accession PM09.812, corresponding to the appearance of a majority of anthocyanins for each accession. These results show that intestinal and colonic microbial digestion of PFSP leads to an accession-dependent pattern for anthocyanin bioaccessibility and degradation.