1. Stephen Collins as Eric Camden, the loving family patriarch and a Protestant minister.
2. Catherine Hicks as Annie Camden, Eric's wife, a homemaker, and a caring mother to their children.
3. Jessica Biel as Mary Camden, the eldest daughter, who later marries her boyfriend, pastor Robbie Palmer.
4. Beverley Mitchell as Lucy Camden, the middle daughter, who is known for her independent and rebellious spirit.
5. Mackenzie Rosman as Ruthie Camden, the youngest daughter, who often provides comedic relief and heartfelt moments.
6. Barry Watson as Matt Camden, the eldest son, who works at his family's auto shop and struggles to find direction in life.
7. David Gallagher as Simon Camden, the second son, who has artistic talents but is also prone to trouble and self-destructive tendencies.
8. Tyler Hoechlin as Martin Brewer, a foster child welcomed into the Camden family, and later becomes a doctor.
9. George Stults as Kevin Kinkirk, a high school athlete who becomes a mentor and friend to the Camden family.
10. Lorenzo Brino as Sam Camden, the youngest son of the Camdens, born at the end of season 10.
Recurring cast members include:
1. Rachelle Lefevre as Ashley, Matt Camden's love interest and later his estranged wife.
2. Adam LaVorgna as Robbie Palmer, Mary's husband and pastor at a youth camp.
3. Ashlee Simpson as Cecilia Smith, a rebellious teenager whom the Camden family takes in as a foster child.
4. Nikolas and Zachary Brino as David and John Camden, the youngest children adopted by the Camdens in the final season.