This paper investigates the fatigue behavior of S135 high-strength drill pipe steel under tension–torsion multiaxial loading. Based on the concept of critical plane during fatigue, the fatigue model under the combined loading of tension–torsion is established. The proposed model is validated, and the predicted results are in good agreement with the experimental testing results. The maximum relative errors between the estimation and the experiment are mostly within the range of factor two to three for proportional, and 90° non-proportional tension–torsion loading. Meanwhile, the failure mechanism is also discussed through fracture analysis.