Characterizing plant genetic resources and understanding the domestication process are key challenges in horticulture. This study focuses on the common grapevine (Vitis vinifera L.), employing molecular, ampelographic, and morphometric techniques to explore its domestication syndrome. We propose a combined domestication index for grape seeds, integrating six commonly used indices. Logistic regression and randomForest machine learning methods were employed to assess the probability of seed domestication. Analysis involved 4029 seeds from 783 samples, spanning live plants (cultivated, wild, feral), archaeological samples, and fossils. Results indicate a distinct domestication syndrome in grapevine seeds, notably characterized by a long stalk (> 1 mm), with combined index values ranging from 0.83 to 1 and domestication probabilities of 0.75 to 1. This syndrome is prevalent in modern cultivars but absent in wild grapevines, aiding in the differentiation of archaeological materials. While not exclusive to Vitis vinifera, the domestication syndrome is characteristic of it, distinguishing it from wild Vitis sylvestris and suggesting isolated domestication events in a few American and Asian Vitis species. Fossil and archaeological materials exhibit low domestication values, hinting at the beginnings of domestication. However, dating reliability remains a challenge.