Human phenotypic variation underpins health outcomes, but defining its molecular basis represents a major biological challenge. Here we introduce “personalised phosphoproteomics”, which links longitudinal physiological measures with subject-specific dynamic phosphoproteome signatures to extract biologically relevant signalling events. We applied this to unravel how exercise potentiates muscle insulin sensitivity by sampling paired muscle biopsies from rested and exercised legs during an insulin infusion alongside muscle-specific in vivo glucose uptake measures. There was considerable individual variance in the phenotypic response to both exercise and insulin and this was mirrored at the level of individual phosphoproteomes. Associations exploiting this variance identified kinases and phosphosites functionally linked with the observed potentiation of insulin action by exercise. Among these were AMPK and mTORC1. Previously thought to be mutually exclusive, AMPK and mTORC1 were both active in the post-exercise state, exhibiting cooperativity through mTORC1 phosphorylation of the AMPK ɑ2 subunit at Serine 377. This study highlights that protein phosphorylation viewed through the lens of dynamic human phenotypic variance can provide mechanistic insights into complex biology, including how exercise promotes insulin sensitivity.