To investigate the effects of general scour on the bearing performance of an anchorage, this study is based on an anchorage project of a sea-crossing bridge and conducts scaled model tests and finite element numerical simulations. In the model tests, homogeneous quartz sand was used to simulate the surrounding soil of the anchorage. Under different scour-depth conditions, three loading schemes were applied: monotonic stepwise loading, monotonic stepwise loading–unloading, and stepwise incremental cyclic loading–unloading, to obtain the load–displacement responses of the anchorage. The results indicate that, in the model tests, for every increase of 0.33H in scour depth (where H denotes the embedment depth of the anchorage), the ultimate bearing capacity of the anchorage decreases by approximately 14.3%, while the influence of different loading modes on the ultimate bearing capacity is relatively small. Based on the experimental results, the finite element modeling approach was validated, and a three-dimensional numerical model of the prototype underwater anchorage was established, considering realistic soil stratification and ground improvement by replacement. The results show that, at the prototype site, when the scour depth increases in increments of 0.2H, the ultimate bearing capacity of the anchorage decreases at a rate of approximately 10.3%. Although slight quantitative differences exist between the prototype numerical results and the scaled model test results, the overall trends are consistent. With increasing scour severity, the failure mode of the anchorage gradually evolves from overturning-dominated failure to overall sliding-dominated failure. Further parametric sensitivity analysis reveals that among the constitutive parameters of the surrounding soil, the internal friction angle has the most significant effect on the ultimate bearing capacity, followed by cohesion, while the influence of the elastic modulus is relatively small.