The capability of operational marine diesel engines to adapt to renewable and low-carbon fuels is considered one of the most influential methods for decarbonizing maritime transport. In the medium and long term, ammonia is positively valued among renewable and low-carbon fuels in the marine transport sector because its chemical elemental composition does not contain carbon atoms which lead to the formation of CO2 emissions during fuel combustion in the cylinder. However, there are number of problematic aspects to using ammonia in diesel engines (DE): in-tensive formation of GHG component N2O; formation of toxic NOx emissions; and unburnt toxic NH3 slip to the exhaust system. The aim of this research was to evaluate the changes in combustion cycle parameters and exhaust gas emissions of a medium-speed Wartsila 6L46 marine diesel engine operating with ammonia, while optimizing ammonia injection intensity within the limits of Pmax, Tmax, and minimal engine structural changes. The high-pressure dual-fuel (HPDF) injection strategy for the D5/A95 dual-fuel ratio (5% diesel and 95% ammonia by energy value) was investigated within the liquid ammonia injection pressure range of 500 to 2000 bar at the identified optimal injection phases (A −10° CAD and D −3° CAD TDC). Increasing ammonia injection pressure from 500 bar (corresponding to diesel injection pressure) in the range of 800–2000 bar determines the single-phase heat release characteristic (HRC). Combustion duration decreases from 90° crank angle degrees (CAD) at D100 to 20–30° CAD, while indicative thermal efficiency (ITE) increases by ~4.6%. The physical cyclic deNOx process of NOx reduction was identified, and its efficiency was evaluated in relation to ammonia injection pressure by relating the dynamics of NOx formation to local combustion temperature field structure. The optimal ammonia injection pressure was found to be 1000 bar, based on combustion cycle parameters (ITE, Pmax, and Tmax) and exhaust gas emissions (NOx, NH3, and GHG). GHG emissions in a CO2 equivalent were reduced by 24% when ammonia injection pressure was increased from 500 bar to 1000 bar. For comparison, GHG emissions were also reduced by 45%, compared to the diesel combustion cycle.