Various forms of exercise induce signaling networks to improve muscle function and confer health benefits. To identify divergent and common signaling networks during and after different exercise modalities, we performed a phosphoproteomic analysis of human skeletal muscle from a cross-over intervention of endurance, sprint and resistance exercise. This identified 5,737 phosphosites regulated during or 3 h after at least one type of exercise modality. We observed striking differences in several signal transduction pathways between the exercise modalities such as divergent signaling of discrete mTORC1 substrates associated with rapamycin sensitivity. We hypothesised defining the core canonical exercise phosphoproteome common to all types of exercise may be a powerful approach to identify novel functional phosphorylation events underlying muscle adaptations and the benefits of exercise. A total of 428 core phosphosites were regulated in all exercise modalities. We prioritised functional phosphorylation via several analyses including pathway/kinase enrichment, machine-learning to identify regulatory phosphorylation events, associating phosphosites to plasma metabolites and overlapping phosphoproteins to human genome-wide association studies. One of these core phosphosites was S67 on the uncharacterized protein C18ORF25 which we validated as an AMPK substrate. Mice lacking C18ORF25 have reduced skeletal muscle fiber-size, exercise capacity and muscle contractile function. Mechanistically, this was associated with reduced PKA signaling and phosphorylation of contractile and calcium handling proteins. Expression of C18ORF25 S66/67D phospho-mimetic using adeno-associated virus reversed the decreased muscle force production. This work defines the divergent and canonical exercise phosphoproteome across different modalities, and identifies C18ORF25 as a regulator of exercise signaling and muscle function.