This study explores a novel multi-injection strategy that combines axis-opposed and single-spray injections to enhance combustion characteristics in a constant volume combustion chamber. In direct-injection internal combustion engines, fuel impingement on the piston and cylinder walls—particularly during cold-start conditions—remains a common challenge. This issue can lead to increased unburned hydrocarbon emissions, greater cooling losses, and reduced thermal efficiency. To address this challenge, a multi-injection system was developed, integrating two pairs of axis-opposed injectors that combine both axis-opposed and single sprays. The core concept of this multi-injection approach is to leverage fuel spray collisions from axis-opposed injections to enhance atomization and mitigate wall wetting. However, conventional axis-opposed injections tend to cause liquid jet and droplet coalescence, which can negatively impact combustion efficiency. Therefore, it is essential to establish a combustion improvement strategy for regions where coalesced droplet groups form. Compared to single-spray and conventional axis-opposed injection systems, the proposed multi-injection strategy promotes droplet atomization and improves fuel-air mixture homogeneity through optimized injector layout and injection timing. Additionally, combustion tests using low-reactivity fuel were conducted to assess the feasibility of this injection strategy under challenging ignition conditions. In-cylinder pressure measurements were analyzed to evaluate the effects of fuel injection conditions and the influence of fuel collision behavior on combustion performance. The results demonstrate that the proposed multi-injection approach is a promising strategy for enhancing combustion efficiency and improving combustion control in advanced engine systems.