Time-dependent system reliability is computed as the probability that the responses of a system do not exceed prescribed failure thresholds over a time duration of interest. In this work, an efficient time-dependent reliability analysis method is proposed for systems with bivariate responses which are general functions of random variables and stochastic processes. Analytical expressions are derived first for the single and joint upcrossing rates based on the first-order reliability method (FORM). Time-dependent system failure probability is then estimated with the computed single and joint upcrossing rates. The method can efficiently and accurately estimate different types of upcrossing rates for the systems with bivariate responses when FORM is applicable. In addition, the developed method is applicable to general problems with random variables, stationary, and nonstationary stochastic processes. As the general system reliability can be approximated with the results from reliability analyses for individual responses and bivariate responses, the proposed method can be extended to reliability analysis of general systems with more than two responses. Three examples, including a parallel system, a series system, and a hydrokinetic turbine blade application, are used to demonstrate the effectiveness of the proposed method.