The objectives of the present study were to develop a simple high performance thin layer chromatography (HPTLC)-based protocol: (i) to allow high-throughput profiling of phenolic compounds of microwaved roots from 295 sweet potato varieties and breeding lines, (ii) to quantify the content of anthocyanins and caffeoylquinic acid (CQA) derivatives, and (iii) to determine their respective contributions to the antioxidant activity of sweet potato methanolic extracts using the DPPH test. Analysed accessions were separated into three groups: white-fleshed (n = 100), orange-fleshed (n = 64) and purple-fleshed (n = 131). Purple-fleshed accessions presented the highest mean CQA content. After DPPH treatment and transmittance scanning of the plate at 517 nm, the most active free radical scavengers were found to be the four CQAs (CGA, 3,4-, 4,5- and 3,5-diCQA) while the anthocyanins were found to be less active. The total antioxidant capacity of the sweet potato methanolic extracts was mostly linked to total CQAs content. This method can now be used for fast routine analysis and selection of sweet potato breeding clones.