As a critical component of railway fastening system, the elastic rail clip (e-clip) maintains the rail position using its specified toe load. To understand its fatigue failure during service, the fatigue experiment, finite element analysis (FEA) and failure analysis were performed on e-clip. Under normal wheel load, e-clips with high, normal, and low toe loads were run-out at 5 × 106 cycles. Under the contribution of impact on wheel load, the fatigue lives were reduced to 5468 cycles and 16,839 cycles for e-clips with high and normal toe loads, respectively. For low toe load, the e-clip under the contribution of impact could withstand >5 × 106 cycles. The stress distribution on e-clip was numerically evaluated using FEA, which was in good agreement with that of experiment. Goodman diagram could be used for the fatigue evaluation of e-clip. The mean stresses and stress amplitudes of run-out e-clips were under the line of Goodman equation, while those of failed e-clips were on and above the line of Goodman equation. The fatigue crack was found to nucleate at the location of highest stress. The severity at fatigue crack front increased with the crack length until the overload fracture.