This research estimates the high-cycle fatigue (HCF) life of integrated concrete bridge installed on water due to temperature changes. To this end, CATIA software was used to geometrically model of a real-scale bridge. Next, thermal–structural coupling analysis was performed by finite element (FE) simulation in ANSYS WORKBENCH software. The comparison technique with experimental data was used to validate the simulation. Afterward, thermal analysis was performed due to air temperature changes in different modes, including the average monthly temperature changes (large variations) as well as the maximum and minimum monthly temperature changes (small variations). The results showed that the most changes in deck length and subsequent maximum deviation in the upper part of steel piles were related to the three warm seasons in the presence of the water. Eventually, a probabilistic approach was employed to find variable amplitude fatigue lifetime of the component based on the number of annual loading blocks. To achieve the high-accuracy response, the effective parameters of the proposed probabilistic approach, including order of Fourier series and the stress range, were optimized automatically. In addition, to obtain HCF behavior of raw material, axial tension–compression fatigue tests were performed on the standard specimens fabricated from steel piles. The results revealed that considering small variations in the calculation of structural fatigue life led to a 550% reduction in life compared to structural analysis due to large variations. In addition, the obtained results were compared with the finite element results.