Branwen first appears in the Second Branch of the Mabinogi, the collection of medieval Welsh prose tales preserved in the White Book of Rhydderch and the Red Book of Hergest. The tale opens at Harlech where Brân the Blessed, high king of Britain, sits with his brother Manawydan and his half-brothers Nisien and Efnisien. Thirteen ships appear from Ireland, and Matholwch, king of that island, comes to ask for Branwen's hand. Brân agrees, seeing a chance for peace, and a great feast is held to celebrate.

The feast is ruined by Efnisien, the dark half-brother whose nature is to cause conflict where none exists. Furious that he was not consulted, Efnisien finds Matholwch's horses and mutilates them, cutting their lips, ears, and eyelids. Matholwch is so insulted that he prepares to sail home, but Brân calms him with gifts: a horse for every horse defiled, a gold plate, a silver rod, and above all the Pair Dadeni, the Cauldron of Rebirth, which can bring the dead back to life though they return without speech. Matholwch accepts and takes Branwen to Ireland.

For a year she is treated with honour, and she bears Matholwch a son named Gwern. But the Irish nobles cannot forget the insult, and they persuade Matholwch that Branwen must be punished. She is stripped of her rank, banished to the kitchens, and beaten every day by the butcher. For three years she endures this, until she finds a way to send word home. She tames a starling, ties a letter to its wing, and sends it flying across the Irish Sea. When Brân reads the message, he gathers an army from the hundred and fifty-four cantrefs of Britain and sails for Ireland.

Brân is a giant, so vast that no house can hold him. When the Irish see him wading through the sea with ships sailing by his shoulder, they think a mountain is coming. Matholwch tries to make peace, building a house big enough for Brân and hanging a hundred flour bags inside, each concealing an armed warrior. Efnisien discovers the trap and crushes every hidden skull. At the feast, Matholwch agrees to make Gwern king, but Efnisien seizes the child and throws him into the fire. Branwen tries to leap in after her son, but Brân holds her back. The war that follows is so terrible that every Irishman is killed except five pregnant women in a cave, and only seven British warriors survive.

The Irish use the Cauldron of Rebirth to revive their fallen, throwing them into the cauldron to emerge whole but mute. Efnisien, seeing this, hides among the corpses and is thrown in with them. From inside he stretches against the sides and shatters the vessel, breaking his own heart. Brân is mortally wounded by a poisoned spear. Knowing he is dying, he orders his men to cut off his head and carry it to the White Hill in London, to be buried facing France so that no enemy shall ever invade Britain from the sea.

The seven survivors, with Branwen and Brân's head, sail back to Wales. They land at Aber Alaw, the mouth of the River Alaw in Anglesey. Branwen looks back toward Ireland and forward toward Britain, and sees the ruin her marriage has caused. She cries: Woe to me that I was born; two fair islands have been laid waste because of me. Her heart breaks, and she dies on the spot. The survivors make her a four-sided grave upon the banks of the Alaw, and the place is called Bedd Branwen to this day. Excavations in the 1960s found the cairn to be a genuine Bronze Age burial mound, with urns containing human ashes, as if the legend had chosen a real ancient grave for its most tragic heroine.