The metabolomic differences in phenolics from leaves derived from 3 artichoke cultivars (Cynara scolymus): American Green Globe, French Hyrious and Egyptian Baladi, collected at different developmental stages, were assessed using UHPLC-MS coupled to chemometrics. Ontogenic changes were considered as leaves were collected at four different time intervals and positions (top and basal) during artichoke development. Unsupervised principal component analysis (PCA) and supervised orthogonal projection to latent structures-discriminant analysis (O2PLS-DA) were used for comparing and classification of samples harvested from different cultivars at different time points and positions. A clear separation among the three investigated cultivars was revealed, with the American Green Globe samples found most enriched in caffeic acid conjugates and flavonoids vs. other cultivars. Furthermore, these metabolites also showed a marked effect on the discrimination between leaf samples from cultivars harvested at different positions, regardless of the plant age. Metabolite absolute quantifications further confirmed that discrimination was mostly influenced by phenolic compounds, namely caffeoylquinic acids and flavonoids. This study demonstrates an effect of artichoke leaf position, regardless of plant age, on its secondary metabolites composition. To the best of our knowledge, this is the first report for compositional differences among artichoke leaves, based on their positions, via a metabolomic approach and suggesting that top positioned artichoke leaves present a better source of caffeoylquinic acids, compared to basal ones.