Juana was the daughter of Juan Manuel, Prince of Villena (1282–1348) and his third wife Blanca Núñez de Lara de La Cerda.^[1] Her mother Blanca (d. 1347) was a descendant of the lords of Biscay and of Lara and of Alfonso X's eldest son, Fernando de la Cerda. She was the last undisputably legitimate member of the House of Ivrea.

Juana's father had been an enemy of King Alfonso XI of Castile, while the king tried to neutralize the Peñafiel family. On 27 July 1350 Juana's brother and guardian, Fernando Manuel of Peñafiel, married her to Henry, an illegitimate son of Alfonso XI.^[1]

In 1361, on the death of her niece Blanca, daughter of her brother Fernando Manuel who himself had died in c. 1350 without other children, she inherited Villena, Escalona and Peñafiel.^{[citation needed]}

Because Juana was a maternal granddaughter of La Palomilla (Juana Núñez de Lara), she also inherited Lara and Biscay.

In 1369, her husband became King Henry II of Castile, after he deposed and murdered his half-brother to take the throne, and she became queen of Castile and León.

When in 1381 she died and left her inheritance to her son, it was finally united with Castile, and ultimately Spain.

• King John I of Castile (1358–1390)
• Eleanor (died 1416)
• Joanna

• Doubleday, Simon R. (2001). The Lara Family: Crown and Nobility in Medieval Spain. Harvard University Press.