Brangaine first appears in the earliest Tristan romances of the twelfth century, in the poems of Thomas of Britain around 1150 and Béroul around 1180, though the legend itself is far older, rooted in Celtic tradition. In Thomas's courtly version, Isolde's mother prepares a love potion and entrusts it to Brangaine with strict instructions: the flask must be kept secret, guarded day and night, and given to Isolde and King Mark to drink on their wedding night, so that their marriage would be bound by a love that could not be broken. Brangaine swore to protect the potion with her life, and kept it close as she boarded the ship to Cornwall.

The voyage was long and the seas were rough. Tristan, who had fetched Isolde for his uncle Mark, shared the cabin with the ladies, trying to comfort her as she wept for the home she was leaving. One evening, when the wind had dropped, a young maid found the golden flask and thought it contained wine. She offered it to Tristan, who passed it to Isolde. They drank together, not knowing they had swallowed a potion that would bind them heart and soul for life. In Béroul's version, the drinking was a simple accident. In Wagner's opera Tristan und Isolde, Brangaine deliberately substituted the love potion for a poison that Isolde had intended for Tristan, unable to let her mistress commit murder. In every version, the result was the same: the two who drank fell into a love stronger than honour, stronger than duty, and stronger than death.

When the ship reached Cornwall, Brangaine performed her second great service. King Mark was eager for his wedding night, and Isolde, no longer a virgin because of what had happened with Tristan on the voyage, could not risk discovery. Brangaine, still a maid, agreed to take Isolde's place in the marriage bed, slipping between the sheets while Isolde hid elsewhere. Mark, in the darkness, never knew the difference, and Isolde's honour was preserved. It was an act of devotion that would have destroyed a lesser woman, but Brangaine gave her body to save her mistress's reputation, and in the morning she returned to her place without a word.

The secret could not be kept forever. As the months passed, Isolde grew suspicious of the woman who knew too much. She feared that Brangaine might reveal the truth about the potion, or worse, that she might have developed feelings for King Mark. In a fit of jealousy, Isolde ordered her servants to take Brangaine into the forest and kill her. The servants led the handmaiden away, but when they reached the woods they found they could not murder the girl who had been so loyal. Instead they tied her to a tree and left her, returning to Isolde with a lie about her death. Isolde, overcome with remorse when she learned the truth, rushed to the forest, freed Brangaine, and begged her forgiveness. The two women were reconciled, though the shadow of that betrayal never fully lifted.

In some later versions, Brangaine's story takes another turn. When Tristan is banished to Brittany and marries Isolde of the White Hands, his brother-in-law Kahedin falls in love not with the queen but with Brangaine. He journeys back to Cornwall in disguise to meet her, and though she uses a magic pillow to put him to sleep before he can dishonour her, the episode shows that Brangaine was more than a servant. She was a woman of beauty and dignity, courted by a knight of Brittany, and worthy of a romance of her own.