Recovering the waste heat of a marine main engine (M/E) to generate electricity was an environmental way to minimize the carbon dioxide emissions for ships, especially with organic Rankine cycle (ORC) technology. The M/E had variable loads and operating times during voyage cycle, which directly affected the ORC thermodynamic potential. In this paper, a voyage cycle-based waste heat utilization from the M/E was introduced to provide reliable evaluation for proposing and designing ORC. The effect of various M/E loads and operating times on ORC performance among three dry-type substances was analyzed. The environmental impact was presented based on the data from one voyage cycle navigation of objective container ship. The results showed that Cyclohexane was capable of net power while Benzene was more suitable for thermal efficiency. The evaporator and condenser were the main irreversible components of the ORC system and required further optimization. Taking the operational profile into consideration, the evaporation pressures were 922–1248 kPa (Cyclohexane), 932–1235 kPa (Benzene) and 592–769 kPa (Toluene), respectively. During the voyage cycle, the carbon dioxide emissions were 99.68 tons (Cyclohexane), 96.32 tons (Benzene) and 60.99 tons (Toluene), respectively. This study provided certain reference for the design and investigation of ORC application to further improve the energy efficiency for container ship.