Al Diablo con los Guapos tells the story of a girl named Milagros, who, at the age 18, leaves the convent where she was raised and finds work at Regina Belmonte, the matriarch of a family company. Regina sympathizes with Milagros immediately but the remainder of the family does not bear her self-assured character and her bad manners.

The son of Constancio Belmonte, Alejandro, is interested in Milagros because of her captivating spirit. Little by little, between suits and discussions, the two begin to date, although Milagros refuses to accept him. She knows Alejandro's reputation of being a womanizer and believes she is going to be abandoned like her mother. Besides this, Alejandro is already engaged.

Constancio Belmonte, Regina's son, detests his family and does not even try hide it. Especially to his wife Luciana, since his father obliged him to marry her which in turn separated him from Rosario, the love of his life. At the time, she was expecting a baby of his, but she disappeared without leaving a trace. As soon as he learned this, Constancio did not try to locate his child who ended up to be Milagros.

Andrea, Alejandro's girlfriend, only wants him for his money, and at the same time is having an affair with Constancio whom she says she loves. Hugo, Alejandro's cousin, is in love with Mili and paints portraits of her that he admires, he also fakes broken leg injury to get closer to her but later confesses his love.

After confessing their love for one another, they are faced with much opposition. Andrea & Hugo make it their mission to separate them, making many plans to ensure that happens. However their plots failed and Alejandro and Milagros are together. But later Alejandro meets Florencia, the daughter of his fathers business partner. They begin to take a liking to each other and eventually go out while Alejandro still harbors feeling for Mili. While this is happening Mili begins to get jealous and then tries to sabotage their relationship which causes all of them to have a fight. But in the end Alejandro is still deeply in love with Mili they try to get married until Alejandro's mother Luciana sabotages their plans. Luciana lies to Mili saying that they are related and reveals that her father is Constancio.

Eventually Mili marries Hugo. Alejandro marries Florencia and they have a little girl, Rosario. Many problems arise in their marriage eventually leaving both Alejandro and Florencia unhappy and miserable. Mili and Hugo are as well unhappy because Hugo wants Mili to love him but she is still in love with Alejandro. Hugo then starts cheating on her with the maid Karla. Mili finds out she is not related to Alejandro and they begin their romance again.

Hugo finally gives Mili a divorce. Florencia leaves Alejandro for her ex-husband while leaving Alejandro with their daughter, Rosario. In the end, Florencia is shot to death by her ex-husband.

Mili's mother Rosario returns to find everyone in shock because she was presumed dead.

Days pass by and Mili marries Alejandro, Karla marries Hugo and Valeria marries Rocky as a triple wedding. then many years later the novel shows how time passes by between the married couples and they start to have kids and grandkids.

At the end, it shows a beach scene with Mili and Alejandro walking together at a very old age while remembering that afternoon that they made love on the beach and suddenly they die together.