Siddalee 'Sidda' Walker (Sandra Bullock) is a writer, and is engaged to be married. On the surface her life appears to be full of promise, but when she makes some comments about her childhood in a magazine interview it exposes all the cracks in her relationship with her mother Viviane 'Vivi' Walker (Ellen Burstyn) along with her own insecurities. Both are as stubborn as each other, and a feud between the two quickly develops.
In her childhood, Vivi was once part of the Ya-Ya Sisterhood a secret group of four girls who swore an oath of friendship. Now the other three Caro, Teensy and Necie step in to try to help Sidda understand her mother by telling her some of the secrets they shared. This they achieve by drugging and abducting her, then introducing her to the Ya-Ya's diary of secrets. The journey to understanding is a long one, and along the way Sidda breaks off her engagement through fear that she will turn out like her mother, still not fully comprehending the influences that made Vivi the way she was. Only by gaining some understanding of her relationship with her mother can Sidda learn to understand herself and decide the direction her own life should take.
The story is told through extensive use of flashbacks to various points in Vivi's life, exploring her relationship with her friends, family, lovers and children.