Long-span cable-stayed bridges are complex systems with numerous components, and prone to failures of multiple components under near-fault ground motions with long-period velocity pulses. The evaluation of dynamic system reliability of cable-stayed bridges is an important challenging issue. In this work, a unified framework for simultaneously determining both the stochastic dynamic responses and system reliabilities of long-span cable-stayed bridges under near-fault stochastic ground motions is proposed based on direct probability integral method (DPIM) with adaptive strategy. Firstly, the 3-dimensional finite element model of typical cable-stayed bridge and the stochastic synthesis model of near-fault ground motions are established. Based on probability density integral equation, new formulas in input probability space of time-variant moments of response are derived. Then, DPIM with adaptive strategy is suggested to calculate the mean value and standard deviation of response via new formulas. Dynamic system reliability of cable-stayed bridge under near-fault stochastic ground motions is evaluated by establishing failure criteria of extreme value mappings of multiple performance functions. Finally, numerical results indicate that the long-period velocity pulse of near-fault motions imposes an important effect, resulting in large mean responses and failure of cables. Failure probability of cables is significantly increased with the occurrence of velocity pulses, which causes the decrease of system reliability of cable-stayed bridge. Thus, the randomness and velocity pulse effect of near-fault ground motions should be seriously considered for reliability-based design and safety assessment of cable-stayed bridges.