In order to clarify the technical and economic boundaries of the combination thickness of chemical flooding layers and injection production well spacing in class III oil layers, and to provide a basis for the upcoming chemical flooding layer combination and well network adjustment in class III oil layers, the principle of profit and loss balance was applied to study the thickness boundaries of layer combination under different conditions of oil price, injection production well spacing, and enhanced oil recovery value. The results showed that under the conditions of increasing oil recovery rate by 10%, injection production well spacing of 125 m, and oil price of 60 $/bbl, when drilling new wells in Block L, the thickness limit of the layer series combination is 13.3 m, and when infilling old wells with an injection production well spacing of 150 m, the limit is 11.2 m. Based on this, chemical flooding layer series combination principles in class III oil layers have been formulated. By applying methods such as reservoir engineering, numerical simulation, and the principle of profit and loss balance, this study aims to investigate the control degree, enhanced oil recovery, injection rate, oil recovery rate, and economic limit well spacing of three types of oil reservoirs in Block L. The results show that when the well spacing is greater than 125 m, the injection rate and oil recovery rate cannot meet the needs of chemical flooding, Moreover, the degree of chemical flooding control and enhanced oil recovery are relatively low; When the well spacing is less than 100 m, the upward trend of improving oil recovery and controlling degree slows down, and it does not meet the economic limit well spacing requirements. Therefore, the reasonable injection and production well spacing for class III oil layers in Block L is determined to be 100–125 m.