The Candy Candy manga provides a "coming of age story" in the shōjo genre. Candy, an abandoned orphan taken in by the orphanage Pony's Home near Lake Michigan around the start of the 20th century,^[4] spent the first years of her life at the orphanage, to where she would often return to repose and to decide her next course in life. When Annie, her best friend at the orphanage, was adopted, she ran outside crying, and met briefly a young man in kilt who told the child not to cry. Candy retained fond memories of the young man and, not knowing his name, remembered him as her "Prince on the Hill". The young man will have great influence and importance in her life later on.

When she turned thirteen, Candy was taken in by the Lagan family as a companion for their Lagan family daughter, Eliza. The Lagans treated her poorly and eventually made Candy a servant girl. When the Lagan family accused Candy of stealing and sent her off to work in their family farm in Mexico, Candy was rescued from being sent to Mexico by William Ardlay, the sole heir of the very wealthy Ardlay family and the owner of the Ardlay estate. William Ardlay became Candy's adoptive father, but his true identity remained a mystery and she would not meet him until the end of the story. He was also the uncle of Candy's first love, Anthony Brown, and a relative of Anthony's cousins, the Cornwell brothers Archibald (Archie) and Alistair (Stear), as well as the Lagan children.

Later on, Anthony died in a hunting accident when he was thrown off the horseback. Thereafter, Candy, along with Archie and Stear, and the Lagan children, were sent to London to attend the prestigious St. Paul's College, a secondary school, where she met the rebellious bad boy Terry Grandchester, the illegitimate child of a British Duke. Terry was her second and grand love (in the words of the author Keiko Nagita/Kyoko Mizuki in the essays found on Misaki's website,^[5] "the great love that cannot bear fruit"). Circumstances divided the pair when Eliza Lagan schemed to have Candy expelled from St. Paul's by manipulating them into a scandal.

After the scandal, Terry left St. Paul's to protect Candy's reputation, but Candy also decided to leave. They would both embark on their individual life journeys forward in America, where Candy trained to become a nurse in Chicago around the time of World War I,^[4] and Terry pursued a career as a rising star actor on Broadway in New York. An actress in his theater troupe, Susanna, became attracted to Terry and believed she loved him. During a rehearsal session, an accident occurred and Susanna saved Terry's life, but in the process became disabled. Her injury destroyed her acting career. Her mother demanded that Terry takes care of her for the rest of her life. Susanna herself became depressed and attempted suicide, knowing that Terry loved Candy and did not love her. Feeling responsible, Terry was torn between reuniting with Candy and his duty to care for Susanna. When Candy discovered what happened, she decided to sacrifice her own happiness and left Terry, so Terry could remain with Susanna, even though Terry did not love Susanna and was deeply in love with Candy.

Afterwards, Candy returned to Chicago to continue her life. By chance, she became the nurse and caretaker to her adoptive father, William Ardlay, who lost his memories after a WWI related bomb explosion on a train in Italy. William ultimately regained his memories and revealed his true identity to Candy. At the end of the story, Candy discovered that he was her childhood Prince of the Hill. In Candy Candy The Final Story Candy discovers that Susanna has died and Terence writes her a letter to say that for him nothing has changed, leaving hope that they will reunite.

There were some plot and character differences between the manga and the anime: Candy's age was different for several events when she grew up at Pony's Home. In the manga, she was six or seven years old when she met her Prince of the Hill, but was ten in the anime. Her sidekick pet raccoon Kurin/Clint belonged solely to the anime version.