| Year | Title | Role | Notes |
|---|---|---|---|
| 1989 | Guiding Light | Elise | |
| 1991 | Darrow | Lillian Anderson | Movie |
| 1992 | Lifestories: Families in Crisis | Mary-Margaret Carter | Episode: "The Secret Life of Mary Margaret: Portrait of a Bulimic" |
| 1997–2002 | Ally McBeal | Ally McBeal | Lead Role (112 episodes) |
| 1998 | The Practice | Ally McBeal | Episode: "Axe Murderer" |
| 2000 | Happily Ever After: Fairy Tales for Every Child | Vanna Van (voice) | Episode: "Rip Van Winkle" |
| 2000 | Saturday Night Live | Herself (host) | Episode: "Calista Flockhart / Ricky Martin" |
| 2001 | Bash: Latter-Day Plays | Sue | Movie |
| 2006–2011 | Brothers & Sisters | Kitty Walker | Lead role (110 episodes) |
| 2014 | Robot Chicken | Dr. Ryan Stone / Smurfette / Rebecca Cunningham (voice) | Episode: "Batman Forever 21" |
| 2014 | Web Therapy | April Keating | Episodes: "Lost on the Young" and "Judicial Oversight" |
| 2015 | Full Circle | Ellen Kelly-O'Rourke | 5 episodes |
| 2015–2018, 2021 | Supergirl | Cat Grant | Series regular (season 1; 20 episodes) Recurring (season 2; 4 episodes) Special guest star (season 3: 1 episode; season 6: 1 episode) |
| 2015 | The Penguins of Madagascar | Doris (voice) | Episode: "The Penguin Who Loved Me" |
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