Vincent married the first of three wives, Helen Huntington, in April 1913. At the ceremony, Vincent was stricken with the mumps, a disease that made him sterile. At the outbreak of World War I, Vincent took advice from his friend and Secretary of the Navy, Franklin D. Roosevelt and joined the Navy. He served overseas with his wife, who did charity work with the YMCA in France. Vincent was promoted from an Ensign to a Leuitenant during the War.
In 1940, Vincent divorced Helen and married Minnie Cushing. In 1953 they divorced and he married Brooke Russell Marshall. Vincent, along with Brooke, whom he called Pookie, developed the Vincent Astor Foundation, a foundation that was designed to give back to New York City. Vincent died in 1959 leaving all of his money to Brooke, surprising many. John Jacob Astor VI, Vincent's half brother who was not yet born when the Titanic sank, contested Vincent's will. John Jacob lost his case, the two had never been on good terms.