This study aimed to investigate the nonlinear structural behavior of concrete deep beams internally reinforced with glass fiber-reinforced polymer (GFRP) reinforcing bars and containing a web opening of various sizes and locations within the shear span. Three-dimensional (3D) numerical simulation models were developed for large-scale GFRP-reinforced concrete deep beams (300 mm × 1200 mm × 5000 mm) with a shear span-to-depth ratio (a/h) of 1.04. Predictions of the numerical models were validated against published experimental data. A parametric study was conducted to examine the effect of varying the opening size and location on the shear response. Results of the numerical analysis indicated that the strength of the deep beam models with an opening in the middle of the shear span decreased with an increase in either the opening width or height. The rate of the strength reduction caused by increasing the opening height was, however, more significant than that produced by increasing the opening width. Placing a web opening in the compression zone close to the load plate was very detrimental to the beam strength. Conversely, a negligible strength reduction was recorded when the web opening was placed in the tension side above the flexural reinforcement and away from the natural load path. Data of the parametric study were utilized to introduce simplified analytical formulas capable of predicting the shear capacity of GFRP-reinforced concrete deep beams with a web opening in the shear span.