Hybrid propulsion and using liquefied natural gas (LNG) as the alternative fuel have been applied on automobiles and some small ships, but research investigating the fuel consumption and emissions over the total voyage of ocean-going cargo ships with a hybrid propulsion and different fuels is limited. This paper tries to fill the knowledge gap by investigating the influence of the ship mission profile, propulsion modes and effects of different fuels on the fuel consumption and emissions of the ship over the whole voyage, including transit in open sea and manoeuvring in close-to-port areas. Results show that propulsion control and electric power generation modes have a notable influence on the ship’s fuel consumption and emissions during the voyage. During close-to-port manoeuvres, propelling the ship in power-take-in (PTI) mode and generating the electric power by auxiliary engines rather than the main engine will reduce the local NOx and HC (hydrocarbons) emissions significantly. Sailing the ship on LNG will reduce the fuel consumption, CO2 and NOx emissions notably while producing higher HC emissions than traditional fuels. The hybridisation of the ship propulsion and using LNG together with ship voyage optimisation, considering the ship mission, ship operations and sea conditions, will improve the ship’s fuel consumption and emissions over the whole voyage significantly.