Her marriage in 1660 with King Louis XIV, her cousin, was made with the purpose of ending the long-standing war between France and Spain.
Unlike France, the kingdom of Spain had no Salic Law, so it was possible for a female to assume the throne. When Maria Theresa's brother Balthasar Charles died in 1646, she became heiress presumptive to the vast Spanish Empire and remained such until the birth of Philip Prospero, in 1657. She was heiress presumptive once more between 1 November and 6 November 1661– the death of Prince Philip and the birth of Prince Charles, who would later inherit the thrones of Spain as Charles II.
In 1658, as war with France began to wind down, a union between the royal families of Spain and France was proposed as a means to secure peace. Maria Theresa and the French king were double first cousins: Louis XIV's father was Louis XIII of France, who was the brother of Maria Theresa's mother, while her father was brother to Anne of Austria, Louis XIV's mother. Anne of Austria desired an end to hostilities between her native country of Spain and her adopted one, France.
The negotiations for the marriage contract were intense. Eager to prevent a union of the two countries or crowns, especially one in which Spain would be subservient to France, the diplomats sought to include a renunciation clause that would deprive Maria Theresa and her children of any rights to the Spanish succession.
A marriage by proxy to the French king was held in Fuenterrabia. Her father and the entire Spanish court accompanied the bride to the Isle of Pheasants on the border in the Bidassoa river, where Louis and his court met her in the meeting on the Isle of Pheasants on 7 June 1660, and she entered France. On 9 June the marriage took place in Saint-Jean-de-Luz at the recently rebuilt church of Saint Jean the Baptist. After the wedding, Louis wanted to consummate the marriage as quickly as possible. The new queen's mother-in-law (and aunt) arranged a private consummation instead of the public one that was the custom.
On 26 August 1660, the newlyweds made the traditional Joyous Entry into Paris. Louis was faithful to his wife for the first year of their marriage, commanding the Grand Maréchal du Logis that "the Queen and himself were never to be set apart, no matter how small the house in which they might be lodging".
Louis and his wife Maria Theresa of Spain had six children from the marriage contracted for them in 1660. However, only one child, the eldest, survived to adulthood: Louis, le Grand Dauphin, known as Monseigneur. Maria Theresa died in 1683, whereupon Louis remarked that she had caused him unease on no other occasion.