Cast
- Jane Seymour — Dr. Michaela Quinn
- Joe Lando — Byron Sully
- Chad Allen — Matthew Cooper
- Erika Flores — Colleen Cooper (up to mid-season 3)
- Jessica Bowman — Colleen Cooper Cook (from season 3 on)
- Shawn Toovey — Brian Cooper
Supporting cast
- J. Leland Adams — Preston A. Lodge III (seasons 4-6)
- Jonelle Allen — Grace
- Barbara Babcock — Dorothy Jennings (seasons 2-6)
- Orson Bean — Loren Bray
- Michelle Bonilla — Teresa Morales (season 5)
- Charlotte Chatton — Emma (season 4-5)
- Frank Collison — Horace Bing
- Brandon Douglas — Dr. Andrew Cook (seasons 4-6)
- Haylie Johnson — Becky Bonner (seasons 1-6)
- Jim Knobeloch — Jake Slicker
- Heidi Kozak — Emily Donovan (season 1)
- Geoffrey Lower — Rev. Timothy Johnson
- Alex Meneses — Teresa Morales Slicker (season 6)
- Henry G. Sanders — Robert E.
- John Schneider — Daniel Simon (season 6)
- Larry Sellers — Cloud Dancing
- William Shockley — Hank Lawson
- Gail Strickland — Ms. Olive Davis (season 1)
- Helene Udy — Myra Bing (seasons 1-4)
- Jennifer Youngs — Ingrid (seasons 1-3)
- Georgann Johnson - Elizabeth Quinn (seasons 2-6)
- Alley Mills - Marjorie Quinn (seasons 2-6)
- Elinor Donahue - Rebecca Quinn Dickinson (season 2-6)
Special Guest Stars
- Edward Albert HI
- David Beecroft
- Verna Bloom
- Guy Boyd
- David Carradine
- Johnny Cash
- June Carter Cash
- Maxwell Caulfield
- Holliston Coleman
- Denise Crosby
- Robert Culp
- Steven Culp
- Jon Cypher
- Jessica Jean Dollarhide
- John Doman
- Zach Galligan
- Blake Gibbons
- Joseph Gordon-Levitt
- Jerry Hardin
- Jerry Haynes
- J.G. Hertzler
- Richard Herd
- James Keach
- Stacy Keach, Sr.
- Matt Letscher
- Anne Lockhart
- Barbara Mandrell
- Richard Moll
- Willie Nelson
- Thomas Ian Nichols
- David Ogden Stiers
- Leland Orser
- Tom Poston
- Andrew Prine
- Fred Rogers
- Kenny Rogers
- Richard Roundtree
- James Sloyan
- Nick Tate
- Susanna Thompson
- Travis Tritt
- Casper Van Dien
- Ray Walston
- Jane Wyman
