Catharina was born in Stockholm on 6 June 1539, the eldest daughter of Gustaf I Eriksson, king of Sweden, and Margaretha Leijonhufvud. As the first Swedish princess in two hundred years, Catharina's birth was seen as a good opportunity to make foreign alliances, and many negotiations were undertaken to see which state would make the best bid; as daughter to a king and a queen who were not born royal, the expectations for her marriage could not be too high, but this disadvantage was partly compensated for with a careful education and a large dowry. Edzard II, Graf von Ostfriesland was chosen because Ostfriesland controlled the important port of Emden, a rival to Lübeck, because it was strategically positioned with Denmark and because Emden was the provider of many Calvinistic craftsmen and artists to Sweden at this point. The negotiations very lengthy, so protracted that Gustaf Vasa pointed out in his anger that it was a blessing his daughter 'neither limped nor was blind'; there was concern in Ostfriesland that the marriage would lead to Swedish domination, and in 1558 Edzard's mother, the dowager-regent Anna von Oldenburg-Delmenhorst, split the power in Ostfriesland between her three sons to prevent this from happening.
In 1559 the wedding of Catharina and Edzard finally took place in Stockholm, but the celebrations were interrupted by the great scandal in Vadstena, where Catharina's beautiful sister Cäcilie was discovered in highly compromising circumstances with Edzard's brother Johannes, who refused to marry Cäcilie and so was imprisoned and possibly castrated as a result. Because of this, the couple could not leave for Ostfriesland until 1561. They had eleven children, of whom Enno III, Johannes and Marie would have progeny.
Catharina Vasa was a well educated Renaissance princess; she was considered an intelligent and learned woman with an independent character and she had a great interest in literature and theology; she was a firm Protestant, visited Wittenberg and wrote interpretations of the bible, and after her husband's death she wrote an ode for his funeral in 1599. She had great influence both on her husband and her sons, she was in contact with her ruling brothers in Sweden through letters and is known to have protested against the marriage of her brother King Johan III to Gunilla Bielke in 1585.
Catharina is considered to be the one of her siblings who bore the closest resemblance to her father. After the death of Edzard II she was regent of what remained of Ostfriesland on behalf of her sons. After her death at Berum on 21 December 1610 the four lordships were united into the lordship of Pewsum, which was inherited by her son Enno III.