Jacob Have I Loved centers around Louise and her relationship with her twin sister, Caroline. Caroline was born sickly and gets more attention than Louise. Caroline takes voice lessons on the mainland and often gets out of doing chores. She belittles Louise, though sometimes unintentionally. She is admired around the island of Rass for her beauty and talent. Louise is often overlooked.
As Louise gets older, she starts to resent Caroline more and more. She reflects on a change that occurs inside her when she is thirteen:
I was proud of my sister, but that year, something began to rankle beneath the pride. Life begins to turn upside down at thirteen. I know that now. But at the time I thought the blame for my unhappiness must be fixed—on Caroline, on my grandmother, on my mother, even on myself. (Chapter 2)
As Louise struggles with resentment toward her sister, the Japanese attack Pearl Harbor and the United States enters the war. Louise faces more adult problems and concerns. A strange man arrives on the island and Louise is suspicious that he is a spy. She is wrong and she befriends the man, who she calls the Captain. She spends time with the Captain and her friend, Call.
Call goes off to fight in World War II. Caroline leaves for music school. Louise feels alone on the island. She decides to leave and attend college herself. She becomes a midwife.