Defects introduced during additive manufacturing currently control fatigue resistance and lead to a large scatter in lifetime, with pancake shaped lack of fusion (LOF) defects being particularly potent. In this study the fatigue crack propagation life of selective laser-melted (SLM) AlSi10Mg alloy is considered in cases where single cracks and multiple cracks can initiate from LOF defects under high cycle fatigue (HCF). Firstly, the aspect ratios of initially long fatigue cracks were determined for critical LOF defects obtained from X-ray CT renderings using the critical defect regularization method, and the response surface method used to obtain the stress intensity factor of the crack front quickly and continuously. Then a single crack propagation model considering the evolution of the crack aspect ratio established to predict the crack propagation life which is in good agreement within in situ X-ray CT imaging of the crack front when a single crack is dominant. The crack propagation phase was predicted to represent 35–60% of the total fatigue life representing a larger fraction at high stress amplitudes. Multiple cracks were found to initiate cracks at the larger stress amplitudes. In cases where multiple cracks arise this is non-conservative and so a synergistic multiple fatigue crack growth (smFCG) model was developed based on multiple defects measured a priori by X-ray CT to depict the competitive cracking effect. Compared with the single crack model, the smFCG model predicts a shorter propagation life (by 5–10%) when multiple defects are involved since it considers all the initial defects within the crack initiation region. Given the propensity of large numbers of defects in AM material this approach may be more appropriate in many cases.