After graduating from South Dade Senior High School in 1968, she enrolled at Miami–Dade Community College, intending to study medicine.

She studied privately with Jean Scott (professor at the Royal Academy of Dramatic Art) in London, and in 1971 moved to Los Angeles.

She won her first film role as Marie Elena, a Mexican mistress, in John Huston's The Life and Times of Judge Roy Bean (1972) (opposite Paul Newman), for which she earned a Golden Globe nomination as Most Promising Newcomer.

She then had a starring role in the risqué comedy film The Naked Ape (1973), which was co-financed by Hugh Hefner, the founder and publisher of Playboy magazine.

She then had ambitions to study at law school and would support herself if needed through small acting roles on television and film, so as to fund her future college tuition.

In 1976, she returned to her character in Earthquake by shooting additional scenes to expand the running time of the original picture for the broadcast premiere of that film, and in 1977, she made a guest appearance on the pilot of the television series Fantasy Island which aired on the ABC network, and in the 1977 television film The Night They Took Miss Beautiful on the NBC network.

When Principal obtained the pilot audition script for Dallas, her academic career ambitions changed, and she decided to return to the full-time acting profession.

As Principal explained to TV Guide Network in 2004, "I had left acting to be an agent and was on my way to law school, but when a friend dropped off a Dallas script, I read it.

"[13] Principal landed the role of Pamela Barnes Ewing on the long-running prime time TV soap opera series Dallas that aired on the CBS network from 1978 to 1991.

Principal left Dallas in 1987, after a two-year decision to prepare with the series' producers for the final season of her character's arc.

[15] She has produced and starred in a half dozen major television productions, including Naked Lie (1989), Blind Witness (1989), and Sparks: The Price of Passion (1990).

Through the late 1990s and in 2000, she continued to appear as a guest star on several TV sitcoms and primetime drama series, including Just Shoot Me!, Family Guy, Providence, and The Practice, as well as appearing as herself on the comedy skit show Tracey Takes On....[26] In 1998, Principal co-starred in the French comedy feature film, Michael Kael vs. the World News Company, written by and starring Benoît Delépine.

The plot centers on a journalist who disrupts the cynical collusion between a CNN-type entity and covert operators in Washington in 1999, at Miami-based international news giant corporation WNC, where star co-anchors Leila Parker (Principal) and James Denit (Atherton) hate each other's guts.

[28] After appearing in NBC's Titans, Principal dedicated her time fully to her skincare company and to philanthropic activities, as she confirmed to People in 2018, "By the time I turned 50, I felt that I wanted to make a change in my life" — she says, of ultimately leaving Hollywood after 2001 — 'My interest had shifted in such a way that would totally pursue my passion, which more and more really was my skincare company and creating products that could help many people.

Principal went on to star in various television films, some of which she produced through her production company, before stepping away to focus on her health and wellness projects.

[15] She has produced and starred in a half dozen major television productions, including Naked Lie (1989), Blind Witness (1989), and Sparks: The Price of Passion (1990).

After 12 weeks on The New York Times Best Seller list in the general non-fiction category, The Body Principal was the first "Advice, How-To, and Miscellaneous" No.

[5][6] In 1981 and 1982, Principal was the recipient of the "Bravo Otto" Award, a German accolade honoring excellence of performers in film, television, and music.

[46] During the filming of The Life and Times of Judge Roy Bean (1972), she dated actor Anthony Perkins, who lost his heterosexual virginity to her.

[52] They celebrated their love in a duet song, "All I Have to Do Is Dream" (1981), a modest pop-chart hit that peaked at number 51 on the Billboard Hot 100 on September 12, 1981.

Principal is particularly involved with ecology, oceans, banning toxic substances, helping children, and rescuing and rehabilitating animals.

Her donations brought together two huge environmental nonprofits, Oceana and Natural Resources Defense Council (NRDC), to work together on the cleanup.

[62] Principal appeared with other celebrities on June 21, 2010, in a CNN Larry King–sponsored telethon to support the Gulf Coast region following the Deepwater Horizon explosion.

[64] On December 13, 2011, Principal donated a substantial sum to the nonprofit marine conservation organization Oceana, and to NRDC to stop the expansion of offshore drilling in the Gulf of Mexico and the Arctic Ocean, fearing such activity could lead to another disastrous oil spill.

[71] In August 2013, she funded in collaboration with Tree People a new mobile system that allows citizens to participate in critical wildfire prevention by texting.

"[73] In August 2014, she fully funded, with the help of Mission K9 rescue, the return of military working dog Maxi from Japan to the United States to be reunited with her former Marine handler.

[76] The following year, she created the Moki fund to help rescue animals and provide medical care so that they can be adopted into permanent homes.

[78] In April 2018, Principal announced that she will double the impact of individual gifts by matching donations to Oceana, up to $50,000 to help protect U.S. coasts from the dangers of offshore oil and gas.

Oceana knows how to win victories for our oceans, and I am making this commitment to encourage people across the country to join me in the fight to protect our coasts.

"[79] In September 2018, Principal donated a fleet of rescue boats to help American Humane with animal disaster relief efforts in the Carolinas after Hurricane Florence.