Astor married Ava Lowle Willing, a prominent socialite from Philadelphia. They had two children: William Vincent Astor (born 1891) and Ava Alice Muriel Astor (born 1902). Their marriage was a significant social event, uniting two prominent families.

Astor and Ava divorced in November 1909. The divorce was a major scandal in New York society, given the couple's prominent status and the reasons behind the split. Ava cited John's neglect and infidelity.

Astor married Madeleine Talmage Force, who was nearly 30 years his junior. The marriage caused considerable controversy due to the age difference and the fact that it occurred relatively soon after his divorce. The couple faced social ostracism from some members of New York society.

John Jacob and Madeleine Astor embarked on a honeymoon trip to Europe, seeking to escape the social scrutiny surrounding their marriage. They traveled to Egypt and France before booking their passage back to America on the Titanic.