She became Henri's companion and lover at the age of 20 and in 1595 her marriage to M. de Liancourt was annulled and Henri gave her the title of Marquise de Monceaux. Although he was legally married to Marguerite de Valois, in public, they were seen as openly affectionate; apart, he wrote her frequent letters. She had a common sense about her and Henri could safely confide his secrets and listen to her advice.
An avid horseback rider, she and Henri enjoyed hunting and riding in the countryside around Paris. For seven years she had the role of a wife and gave the King three children he willingly acknowledged. Seeking power, she used her position to help persuade him to convert from Protestantism to Catholicism in order to obtain the throne of France.
Henri purchased the Duchy of Beaufort for her in 1597. After applying to Pope Clement VIII for a divorce and authority to remarry, in March of 1599 Henri gave her his coronation ring. In early April of that year, King Henri was at the Royal Chateau Fontainebleau when news arrived that Gabrielle was gravely ill, having given birth prematurely to King Henri's stillborn son. On April 10, 1599, while on his way to her, another messenger delivered the news of her death.
A grief-stricken king gave Gabrielle the funeral of a Queen, her coffin transported amidst a procession of princes, princesses, and nobles to the Saint Denis Basilica for a requiem Mass. Known in French history and song as La Belle Gabrielle, she was interred at Notre Dame la Royale, Maubuisson, Doubs, Franche-Comté.
A publication after her death called the "Mémoires secrets de Gabrielle d'Estrée" (The Secret Memoirs of Gabrielle d’Estrée) is believed to have been written by one of her friends.
In 1626, her son César (b. June 1594), the Duke of Vendome, participated in a plot against Cardinal Richelieu. César was captured and held in prison for three years. In 1641 he was accused of conspiracy again and this time fled to England.