Candidatus Phytoplasma pruni is the causative agent of X-disease on peach (Prunus persica) trees. Infected trees exhibit premature yellowing, leaf necrosis causing a shot-hole appearance, limb dieback, and eventual death. How pathogen infection leads to these symptoms is unknown. This study undertook a modern characterization of the disease by assessing the physiological and transcriptomic consequences of phytoplasma infection. Phytoplasma titer was high in the symptomatic tissues and undetected or at low titer in asymptomatic tissues. Symptomatic leaves had a significant decrease in chlorophyll a, chlorophyll b, and carotenoids. Transcriptomic analysis showed alterations in genes related to phytohormone synthesis and signaling, circadian rhythms, lignification, and sugar synthesis and transport. Several transcripts that may be related to symptom development were identified. Collectively these data give a much clearer picture of symptom development in Ca. P. pruni infected P. persica and provide several avenues of further research in determining how Ca. P. pruni interacts with its host to elicit the observed symptoms.