Out of Africa tells the story of a farm that the narrator once had in Africa. The farm is located at the foot of the Ngong hills outside of Nairobi, in what is now Kenya. It sits at an altitude of six thousand feet. The farm grows coffee, although only part of its six thousand acres is used for agriculture. The remaining parts of the land are forest and space for the natives to live on.

Most of the natives on the farm are from the Kikuyu tribe. In exchange for living on the farm, they labor on it a certain number of days per year. There are many other tribal Africans nearby. The Swahilis live in Nairobi and down the coast. The Masai live on a large Reserve just South of the farm. Many Somalis live in the area as well, including Farah, the chief servant who helps the narrator run the entire farm. The narrator herself is a Danish woman. She never gives her name while telling her story, although it is mentioned in subtle ways as "Baroness Blixen" and once as "Tania."

The narrator is actively involved with the natives on her farm. She runs an evening school for both children and adults. She gives medical care to anyone who needs it every morning. Once she treats a young Kikuyu boy Kamante, who has open sores running up and down his legs. When she cannot heal him, she sends him to a nearby hospital runs by Scotch Protestants. Kamante is healed and returns home a newly converted Christian. He becomes the farm chef and is an expert at preparing the most complex of European dishes. The narrator even sends him for further training in Nairobi.

For the majority of Out of Africa, the narrator remembers different incidents that took place on the farm, although these events are not described in chronological order. One time there is an accidental shooting in which one native boy shot two others, killing one and seriously injuring the other. Eventually, the elders of the Kikuyu tribe determine that the father of the boy who shot the gun must pay the other families for what they suffered. After numerous debates and the involvement of the Kikuyu Chief, Kinanjui, a certain quantity of livestock is settled upon.

The narrator also has many visitors to her farm. These visitors include many Europeans living around Nairobi, natives who come for large native dances or Ngomas, a old Dane named Knudsen who lives out his days on the farm, and an Indian high priest. Two of her closest friends, Berkeley Cole and Denys Finch-Hatton, spend a large amount of time on the farm. Berkley Cole has his own nearby farm, but he helps keep the narrator's up to standard by bringing in wine, food, and gramophone records. Denys Finch-Hatton has no home in Africa except for the farm, although he spends most of his days on safari. Finch-Hatton and the narrator frequently hunt together. On two separate occasions, they shot two lions together. Finch-Hatton and the narrator have a special relationship. Although the narrator never specifically states that the two are lovers, such a relationship is implied.

As the narrator weaves through her memories of Africa, she shapes a landscape that resembles a type of paradise. On her own farm, she lives in unity with the natives and even some of the animals. At one point, a domesticated deer, Lulu, comes to live with them, which symbolizes the connection of the farm to its landscape. The narrator in general proposes that Africa is superior to Europe because it exists in a more pure form, without the modernizing influence of culture. As such it is closer to what God initially intended, when he created man, it appears like a true paradise.

After describing life on her African farm as idyllic, the narrator concludes the tale in tragic tones. The coffee farm goes bankrupt because of the difficulties of growing at such a high altitude. When the bills cannot be paid, the narrator sells the farm to a foreign firm who plan to divide it up for residential development.

Soon after the farm is sold, another tragedy strikes. Denys Finch-Hatton is killed when his airplane crashes south of Nairobi. The narrator has him buried on the Ngong Hills at a location that looks over the plains. Eventually, Denys's brother, the Lord Winchilsea, places a large obelisk on the grave. It is inscribed with the "Rime of the Ancient Mariner." Two lions additionally come to later sit on Finch-Hatton's grave, a fact that the narrator finds symbolically fitting given Denys's nobility and character.

Before she leaves Africa, the narrator also works to relocate the natives who live on her farm, since the new owners want them to leave. After much effort, the colonial government agrees that they can all move to a portion of the Kikuyu Reserve. With her affairs settled, the narrator herself leaves Africa after selling her furniture, giving away her animals, and telling all of her friends good-bye.