A criterion is developed which predicts matrix fatigue crack initiation for Uni-Directional (UD) composite plies subjected to multiaxial fatigue load at all stress-ratio's: Tension-Tension, Compression-Compression and Tension-Compression. This research is based on physical observations of matrix damage types and their respective driving forces. Existing fatigue prediction formulations, that partly succeed in predicting fatigue life to initiation, are investigated for their key attributes which are subsequently combined in a coherent way. The framework requires 7 material parameters: 4 for Tension-Tension load, 2 for Compression-Compression load and 1 to take into account the accelerated occurrence of damage under Tension-Compression load. The material parameters can be calibrated from only 7 crack initiation S-N curves. 5 experimental datasets, a variety of the two most common reinforcing fibres and matrix (Carbon and Glass fibres combined with an epoxy or PEEK resin), are selected for a thorough verification and validation of the criterion. The agreement of the prediction with experiment is, remarkably, excellent for Glass/Epoxy, good for Carbon/Epoxy and reasonable for Carbon/PEEK. This new framework establishes a solid base for further developments to predict matrix crack initiation and the inclusion of other failure types such as fibre kinking.