The structural response of the main components of offshore wind turbines (OWTs) is considerably sensitive to amplification as their excitation frequencies approach the natural frequency of the structure. Furthermore, uncertainties present in the loading conditions, soil and structural properties highly influence the dynamic response of the OWT. In most cases, the cost of the structure reaches around 30% of the entire OWT because conservative design approaches are employed to ensure its reliability. As a result, this study aims to address the following research question: can the structural reliability of OWT under fatigue loading conditions be predicted more consistently? The specific aims are to (1) establish the design parameters that most impact the fatigue life, (2) determine the probability distributions of the design parameters, and (3) predict the structural reliability. An analytical model to determine the fatigue life of the structure under 15 different loading conditions and two different locations were developed. Global sensitivity analysis was used to establish the more important design parameters. Also, a systematic uncertainty quantification (UQ) scheme was employed to model the uncertainties of model input parameters based on their available information. Finally, the framework used reliability analysis to consistently determine the system probability of failure of the structure based on the fatigue limit state design criterion. The results show high sensitivity for parameters usually considered as deterministic values in design standards. Additionally, it is shown that applying systematic UQ produces a better approximation of the fatigue life under uncertainty and more accurate estimations of the structural reliability. Consequently, more reliable and robust structural designs may be achieved without the need for overestimating the offshore wind turbine response.