Originally titled Her Royal Highness Princess Maria Christina of Naples and Sicily, on 18 December 1816 her title was changed to Princess Maria Christina of the Two Sicilies when her father changed the name of his kingdom. Her Spanish name was María Cristina de las Dos Sicilias.

Born in Palermo, Sicily, Italy on 27 April 1806, she was the daughter of King Francis I (In Italian, Francesco I) of the Two Sicilies by his second wife, Maria Isabella of Spain. She also descended from the Austrian Habsburgs as her grandmother was Queen Marie Caroline and her grand aunt was Marie Antoinette.

Maria Christina married King Ferdinand VII of Spain on 11 December 1829 in Madrid. Ferdinand was her uncle by birth and by marriage. Like her mother Maria Isabella, Ferdinand was a child of King Charles IV of Spain (Carlos IV in Spanish) and his wife, Maria Luisa of Parma. With the death of King's third wife on 27 May 1829, Ferdinand's desperation to father an heir for his crown resulted in his fourth marriage just seven months later.

The new queen, Maria Christina, rapidly gave birth to two daughters, Isabella (the future Queen Isabella, 1830 – 1904) and the Infanta Doña María Luísa Fernanda (1832 – 1897). When Ferdinand died on 29 September 1833, Maria Christina became regent for their daughter Isabella. Isabella's claim to the throne was disputed by her uncle, the Infante Don Carlos María Isidro Benito, Count de Molina, who claimed that his brother Ferdinand had unlawfully changed the succession law to permit females to inherit the crown (Carlism). Some supporters of Don Carlos went so far as to claim that Ferdinand had actually bequeathed the crown to his brother but that Maria Christina had suppressed that fact. It was further alleged that the Queen had signed her dead husband's name to a decree recognizing Isabella as heir.

Carlos' attempt to seize power resulted in the Carlist Wars. Despite considerable support for Carlos from the Roman Catholic Church and conservative elements in Spain, Maria Christina successfully retained the throne for her daughter. The Carlist Wars grew from a dispute about the succession into a dispute over the future of Spain. The supporters of Maria Christina and her daughter favored a liberal constitution and progressive social policies. In contrast, Carlos' supporters (called Carlists) favored a return to traditional society and an absolute monarchy. Ultimately, the army's loyalty to Isabella II proved the decisive issue in the war.

On 28 December 1833, shortly after the death of Ferdinand VII, Maria Christina had secretly married an ex-sergeant from the royal guard, Agustín Fernández Muñoz, Duke of Riansares (1808 – 1873). Muñoz was given the title Duke of Riansares. Maria Christina and Muñoz had several children together while trying to keep their marriage a secret.

Eventually, news of Maria Christina's marriage to this low-ranking soldier became public. That news made the Duchess of Riansares deeply unpopular. Her position was undermined by news of her remarriage and concerns that she was not actually supportive of her liberal ministers and their policies. Eventually, the army, which was the backbone of Isabella II's support, and the liberal leadership in the Cortes combined to demand that Maria Christina stand aside from the regency. In 1840, the army commander, General Baldomero Espartero, Count of Luchana, replaced her as regent.

The new government required the ex-regent to leave Spain. After an unsuccessful attempt to return to power, Maria Christina retired permanently to exile in France after 1844. France remained her primary residence for the remainder of her life.

A revolution forced daughter Isabella II from her throne on 30 September 1868 and she joined her mother in exile in France. Isabella II renounced the throne in favor of her son, Alfonso XII, on 25 June 1870. Supporters of Alfonso XII made it clear that neither his mother nor grandmother could play an active role in the effort to restore the monarchy. When Alfonso XII regained the Spanish crown on 29 December 1874, Maria Christina and Isabella II were permitted to return to Spain as visitors but denied permission to live there permanently. Neither was allowed to exercise influence in the Spanish government.

The marriage to Muñoz and the events of Maria Christina's turbulent regency drove a permanent wedge between her and her Spanish royal offspring. Neither Isabella II nor Alphonso XII had much interest in a relationship with the former Queen Regent. Maria Christina died in Le Havre, France on 22 August 1878. As the widow of Ferdinand VII and the mother of Isabella II, Maria Christina was buried in the royal crypt of El Escorial monastery.