The only son of King Philip IV of Spain and his first wife, Elisabeth of France, Balthasar Charles was born in the Royal Palace of Madrid on 17 October 1629.

[11] Queen Elisabeth played a significant role in Balthasar Charles's upbringing and education, encouraging the prince to develop interests in music and theatre.

[13] She fell ill in October 1644 and would not allow Balthasar Charles or his sister, Maria Theresa, to approach her on her deathbed, stating, "There are plenty of Queens for Spain, but Princes and Princesses are rare".

[15] His father soon began diplomatic efforts to seek a bride for the prince: Archduchess Mariana of Austria, daughter of Holy Roman Emperor Ferdinand III and his paternal aunt, Maria Anna, and therefore his cousin, was chosen; they were betrothed in 1646.

[16] Another cousin, the daughter of his mother's sister, Henrietta Maria and her husband, King Charles I of England, Mary, Princess Royal, was also proposed as a potential bride,[17] but nothing materialized due to religious differences.

[23] On October 7, the king wrote to his spiritual advisor, Sister Maria de Agreda, that the prince was suffering from severe fever and delirium, believed to be symptoms of smallpox.

[15] The king, facing mounting pressure to remarry for the sake of securing a male heir, consented to a second marriage with his son's former bride-to-be, Mariana of Austria.