Taking a T300k VLCC oil tanker as the research object, the ship route estimation model with minimum fuel consumption, CO2 emissions and shortest ETA as the objective function is established, which considers the weather conditions and constraints of the main engine rated power and safety comprehensively. On the basis of model verification, combined with the weather forecast data and the current maritime market conditions, the estimation indicators were analyzed. The research results show that, prefabricated Route 1 and 2 were the shortest ETA and the minimum fuel consumption routes respectively, although the prefabricated Route 1 saved 36.58 h compared with the prefabricated Route 2, the fuel consumption and CO2 emissions of the prefabricated Route 2 were reduced by 0.94 t/h and 2.92 t/h, and under the shortest ETA objective function, if keeping the initial speed, the main engine would be limited by rated power when the ship encounters Beaufort number≥4 headwind or bow wind. Accordingly, the ship route estimation method comprehensively considering weather conditions and constraints can analyze the variation rules of the fuel consumption, speed loss, CO2 emissions and costs of multiple prefabricated routes under different objective functions, which can provide decision support for shipping companies to improve operation economy.