Macrina was born in 327 in Cesarea, the eldest child of Basil and Emmelia. She was the granddaughter of St. Macrina the Elder and sister of St. Basil, St. Gregory of Nyssa, and St. Peter of Sebastea. Her mother based herself on the Book of Wisdom of Scriptures to raise her children, and used to chant the psaltery with them.
At age 12, Macrina was engaged to be married, but when her fiancé died, she decided she would not marry. She dedicated her life to help raise her brothers well and to assist her mother. After her siblings had grown up and were completely formed, they used to call her Macrina the Great, as they had in their childhood, a sign of the high respect they had for her.