Each of the six Readers contains a series of passages for students to read. The early Readers include a list of new vocabulary words before each story, with pronunciation guides. By the third Reader, these lists are gone, and the emphasis shifts to articulation and pronunciation. The final three readers slowly add more advanced concepts such as reading verse, pauses and inflection.

In addition to containing practical lessons on spelling, McGuffey's passages and examples were chosen with the goal of providing moral instruction as well. They would provide obvious role models or cautionary tales designed to steer students to what McGuffey, a Presbyterian minister, saw as the correct moral path.

Through the sheer number of copies sold of McGuffey's Readers, and the length of time they remained in use, he may have had more influence upon American culture than any other educator in history. Philip Shriver, a historian associated with Miami University, credits the McGuffey Readers with popularizing "Mary Had a Little Lamb," "The Boy Who Cried Wolf," and even certain sayings - for example, "Where there's a will, there's a way."

Although McGuffey's Readers fell out of fashion in the early twentieth century, they still have a small following, even today, and can be found in use in some school districts in West Virginia and Virginia.