As a promising solution to reduce the carbon emissions from internal combustion engines, ammonia has received widespread attentions. However, many challenges in ammonia engines are still difficult to overcome. The highpressure direct-injection ammonia/diesel dual-fuel (HPDF) combustion mode is expected to promote ammonia combustion and reduce greenhouse gas emissions, thus received widespread attentions. The fuel injection spatial and temporal arrangements of HPDF combustion mode were fully investigated in this paper, focusing on the ammonia ignition mechanism, combustion characteristics, working efficiency, nitrogen oxide generation and unburned ammonia emissions. Injection spatial arrangement exhibits significant impacts on ignition mechanism and combustion characteristics of HPDF combustion mode. The single dual-fuel injector method can significantly improve the combustion efficiency and indicated thermal efficiency (ITE) compared to the two-injector method due to the more efficient ignition of ammonia and higher combustion rate. The single-injector method has lower N2O emissions, which is conducive to greenhouse gas reduction, although its NOx emissions are higher than that of the two-injector method. ITE and NOx emissions increase with ammonia injection timing advanced, while the N2O and unburned NH3 emissions both increase significantly with over-advanced or over-delayed ammonia injection timings. Based on the constraints of maximum pressure limit and Euro 7 regulation, an optimized operating range for the HPDF ammonia engine was obtained. The optimization analysis results show that the HPDF ammonia engine reaches ITE of 51.26% while maintaining low NOx, N2O and NH3 emissions.