The stories in A Wonder-Book for Girls and Boys are all stories within a story, the frame story being that a Williams College student, Eustace Bright, is telling these tales to a group of children at Tanglewood, an area in Lenox, Massachusetts, where Hawthorne lived for a time. All the tales are modified from the original myths.

A Wonder-Book for Girls and Boys covers the myths of

The Gorgon's Head - recounts the story of Perseus killing Medusa at the request of the king of the island, Polydectes.

The Golden Touch - recounts the story of King Midas and his "Golden Touch".

The Paradise of Children - recounts the story of Pandora opening the box filled with all of mankind's Troubles.

The Three Golden Apples - recounts the story of Heracles procuring the Three Golden Apples from the Hesperides' orchard, with the help of Atlas.

The Miraculous Pitcher - recounts the story of Baucis and Philemon providing food and shelter to two strangers who were Zeus and "Quicksilver" (Hermes) in disguise. Baucis and Philemon were rewarded by the gods for their kindness; they were promised never to live apart from one another.

The Chim ra - recounts the story of Bellerophon taming Pegasus and killing the Chim ra.

The book includes the myths of:

Theseus and the Minotaur (Chapter: "The Minotaur")

Antaeus and the Pygmies (Chapter: "The Pygmies")

Dragon's Teeth (Chapter: "The Dragon's Teeth")

Circe's Palace (Chapter: "Circe's Palace")

Proserpina, Ceres, Pluto, and the Pomegranate Seed (Chapter: "The Pomegranate Seed")

Jason and the Golden Fleece (Chapter: "The Golden Fleece")

Hawthorne wrote an introduction, titled "The Wayside", referring to The Wayside in Concord, where he lived from 1852 until his death. In the introduction, Hawthorne writes about a visit from his young friend Eustace Bright, who requested a sequel to A Wonder-Book, which impelled him to write the Tales. Although Hawthorne informs us in the introduction that these stories were also later retold by Cousin Eustace, the frame stories of A Wonder-Book have been abandoned.

Hawthorne wrote the first book while renting a small cottage in the Berkshires, a vacation area for industrialists during the Gilded Age. The owner of the cottage, a railroad baron, renamed the cottage "Tanglewood" in honor of the book written there. Later, a nearby mansion was renamed Tanglewood, where outdoor classical concerts were held, which became a Berkshire summer tradition. Ironically, Hawthorne hated living in the Berkshires.

The Tanglewood neighborhood of Houston was named after the book. The book was a favorite of Mary Catherine Farrington, the daughter of Tanglewood developer William Farrington. It reportedly inspired the name of the thickly wooded Tanglewood Island in the state of Washington.