Reducing carbon emissions from internal combustion engines has become a crucial topic due to the pressure brought about by global warming. Ammonia, a carbon-free fuel, has significant potential for heavy-duty diesel engine applications. However, the laminar flame speed of ammonia fuel is relatively slow, resulting in suboptimal combustion performance. Therefore, the present study focuses on ammonia-diesel dual-fuel heavy-duty engines. A novel liquid ammonia high-pressure direct injection (HPDI) strategy has been developed to address the challenges associated with poor combustion performance and increased unburned ammonia emissions in ammonia-diesel dual-fuel internal combustion engines. Firstly, a three-dimensional numerical simulation method was utilized to establish and verify a model of a heavy-duty internal combustion engine that incorporates HPDI of liquid ammonia. Afterward, numerical studies comparing the engine's combustion and emission characteristics are conducted with varied ammonia energy fractions, liquid ammonia injection timings, and liquid ammonia injection directions. The results indicate that, compared to the pure diesel mode, the novel liquid ammonia HPDI strategy can alter the combustion mode, significantly improving fuel–air mixture efficiency. This leads to more thorough combustion. After replacing 80% of the fuel energy input with ammonia, there is still an increase of 8.9% in indicated mean effective pressure and a 10.6% improvement in indicated thermal efficiency. Moreover, modifying the HPDI strategy reduces greenhouse gas emissions effectively, and due to the thermal de-NOx reaction, there is a notable decrease in NOx emissions. Furthermore, by altering the liquid ammonia injection timing and direction, finer control of fuel combustion and pollutant generation can be achieved, thereby reducing unburned ammonia emissions in conditions of high ammonia energy fractions.