The cross-section warping effect and warping-induced long-term prestress loss due to creep are investigated in this paper. Both phenomena were analyzed deterministically and stochastically. The random character of concrete creep and environmental factors have substantial effects on the statistical scatter of the total prestress loss. To obtain the real development of concrete long-term performance, sophisticated models for concrete creep and shrinkage prediction were used. The Monte Carlo–Latin hypercube sampling method was applied to capture the statistical variability of boundary and environmental conditions. It is shown that the severity of cross-section warping can be important, particularly in the case of short spans and unevenly distributed and isolated tendons in a cross section. The three-dimensional effects and the statistical variability of creep are considered to enable reliable design of box girder bridges.