The present investigation focuses on the response of simply supported reinforced concrete rectangular-section beams with multiple openings of different sizes, numbers, and geometrical configurations. The advantages of the reinforcement concrete beams with multiple opening are mainly, practical benefit including decreasing the floor heights due to passage of the utilities through the beam rather than the passage beneath it, and constructional benefit that includes the reduction of the self-weight of structure resulting due to the reduction of the dead load that achieves economic design. To optimize beam self-weight with its ultimate resistance capacity, ten reinforced concrete beams having a length, width, and depth of 2700, 100, and 400 mm, respectively were fabricated and tested as simply supported beams under one incremental concentrated load at mid-span until failure. The design parameters were the configuration and size of openings. Three main groups categorized experimental beams comprise the same area of openings and steel reinforcement details but differ in configurations. Three different shapes of openings were considered, mainly, rectangular, parallelogram, and circular. The experimental results indicate that, the beams with circular openings more efficient than the other configurations in ultimate load capacity and beams stiffness whereas, the beams with parallelogram openings were better than the beams with rectangular openings. Commonly, it was observed that the reduction in ultimate load capacity, for beams of group I, II, and III compared to the reference solid beam ranged between (75 to 93%), (65 to 93%), and (70 to 79%) respectively.