Esca is a destructive disease in grapevines (Vitis vinifera L.) caused by at least three fungi and characterised by two different external symptoms, the apoplectic and leaf stripe form. This latter form can be discerned as soon as symptoms become visible, but the preceding discrete signs during incubation are poorly or not understood. To further understand the development of the leaf stripe form, the period preceding and following the appearance of symptoms was investigated by studying physiological and molecular markers associated with photosynthetic mechanisms and stress response. No perturbation of any targeted metabolism was observed in asymptomatic leaves of asymptomatic canes from vines showing the leaf stripe form of esca. Conversely, drastic alterations of photosynthesis functions were registered in presymptomatic leaves, as revealed by the decrease of gas exchange and chlorophyll fluorescence, and the repression of photosynthesis-related genes. These alterations were amplified during symptom development. Expression of defence-related genes was affected and detected early in presymptomatic leaves and amplified during symptom expression. Our results suggest that grapevines may react precociously by reducing photosynthesis and triggering defence mechanisms in response to the leaf stripe form of esca.