In time-dependent reliability analysis, the first-passage method has been extensively used to evaluate structural reliability under time-variant service circumstances. To avoid computing the outcrossing rate in this method, surrogate modeling may provide an effective alternative for calculating the time-dependent reliability indices in structural analysis. A novel approach, namely time-dependent reliability analysis with response surface (TRARS), is thus introduced in this paper to estimate the time-dependent reliability for nondeterministic structures under stochastic loads. A Gaussian stochastic process is generated by using the expansion optimal linear estimation (EOLE) method which has proven to be more accurate and efficient than some series expansion discretization techniques. The random variables and maximum responses of uncertain structures are treated as the input and output parameters, respectively. Through introducing the response surface (RS) model, a novel iterative procedure is proposed in this study. A Bucher strategy is adopted to generate the initial sample points, and a gradient projection technique is used to generate new sampling points for updating the RS model in each iteration. The time-dependent reliability indices and probabilities of failure are thus obtained efficiently using the first-order reliability method (FORM) over a certain design lifetime. In this study, four demonstrative examples are provided for illustrating the accuracy and efficiency of the proposed method.