Set in the 1960s and 1970s, Meridian centers on Meridian Hill, a student at the fictitious Saxon College, who becomes active in the Civil Rights Movement. She becomes romantically involved with another activist, Truman Held. They have a turbulent on-and-off relationship, during which she becomes pregnant by him.

After Meridian has an abortion, Truman becomes far more attached to her and longs for them to start a life together. Later, Truman becomes involved with a white woman, Lynne Rabinowitz, who is also active in the Civil Rights struggle, though perhaps for the wrong reasons.

As time passes, Truman attempts, unsuccessfully, to achieve personal and financial success while Meridian continues to stay involved in the movement and fight for issues she believes deeply in.