Born Annie Carmichael on January 26, 1923, in Goldsboro, North Carolina, Jeffreys entered the entertainment field at a young age, having her initial training in voice (she was an accomplished soprano). "She became a member of the New York Municipal Opera Company on a scholarship and sang the leades at Carnegie Hall in such things as La bohème, Traviata, and Pagliacci." However, she decided as a teenager to sign with the John Robert Powers agency as a junior model.
Her plans for an operatic career were sidelined when she was cast in a staged musical review, Fun for the Money. Her appearance in that revue led to her being cast in her first movie role, in I Married an Angel (1942), starring Nelson Eddy and Jeanette MacDonald. She was under contract to both RKO and Republic Studios during the 1940s, including several appearances as Tess Trueheart in the Dick Tracy series, and the 1944 Frank Sinatra musical Step Lively. She also appeared in the horror comedy Zombies on Broadway with Wally Brown and Alan Carney in 1945 and starred in Riffraff with Pat O'Brien two years later. Jeffreys also appeared in a number of western films and as bank robber John Dillinger's moll in 1945's Dillinger
When her Hollywood career faltered, she instead focused on the stage, playing lead roles on Broadway in productions such as the 1947 opera Street Scene, the 1948 Cole Porter musical Kiss Me, Kate (having replaced Patricia Morison) and the 1952 musical Three Wishes for Jamie. With long-term husband Robert Sterling, who was first married to Ann Sothern, she appeared in the CBS sitcom Topper (1953–1955), in which she was billed in a voiceover as "the ghostess with the mostest".
On December 18, 1957, Jeffreys and her husband played a couple with an unusual courtship arrangement brought about by an attack of the fever in the episode "The Julie Gage Story", broadcast in the first season of NBC's Wagon Train.
After a semi-retirement in the 1960s, she appeared on television, appearing in episodes of such series as Love, American Style (with her husband), L.A. Law and Murder, She Wrote. She was nominated for a Golden Globe for her work in The Delphi Bureau (1972). From 1984 to 1985, she starred in the short-lived Aaron Spelling series Finder of Lost Loves. She also appeared in Baywatch as David Hasselhoff's mother, and also had a recurring role in the night-time soap Falcon Crest as Amanda Croft.
In 1979, she guest starred as Siress Blassie in the Battlestar Galactica episode "The Man with Nine Lives" as a love interest of Chameleon, a part played by Fred Astaire. She was the last person to dance with him onscreen. She also guest starred as Prime Minister Dyne in the Buck Rogers in the 25th Century episode "Planet of the Amazon Women" as the leader of the titular planet.
Her most recent career has been in daytime television; From 1984 to 2004, she appeared on the soap opera General Hospital (as well as its short-lived spinoff, Port Charles) in the recurring role of wealthy socialite Amanda Barrington, a long-time board member of both the hospital and ELQ. In her initial storyline, she was part of a blackmail scheme which led to the murder of Jimmy Lee Holt's mother, Beatrice, of whose death she was a suspect in. In the last year of "Port Charles", Amanda briefly became a vampire after being attacked. The character last appeared on screen in 2004 when Amanda attended Lila Quartermain's funeral.
Jeffreys' star in the Television category on the Hollywood Walk of Fame is at 1501 Vine Street. It was dedicated February 8, 1960. In 1997, she was a recipient of a Golden Boot Award as one who "furthered the tradition of the western on film and in television." In 1998, she received the Living Legacy Award from the Women's International Center.
Jeffreys has been married twice. Her first marriage, to Joseph Serena, was annulled in 1949. They had no children.
She married actor Robert Sterling in 1951. Sterling appeared with Jeffreys in the series Topper. In January 1958, the duo attempted to star in another series, Love That Jill. It ran only a few months, with 13 episodes shot.
They had three sons: Jeffrey, Dana and Tyler. Robert Sterling died on May 30, 2006 at age 88.
In July 1956, Jeffreys' mother, Kate Jeffreys Carmichael, 67, was run down and killed by her own automobile in the driveway of the home of her daughter. Police said Carmichael was taking books from the car's trunk when the emergency brake apparently slipped. The car rolled down the sloping driveway, dragging the actress' mother 26 feet.Topper (1953-1955)
Dearest Enemy (1955)
Love That Jill (1958) (canceled after 13 episodes)
Two's Company (1965) (unsold pilot)
Bonanza (1966) episode "Unwritten Commandment" (Lilly)
The Man from U.N.C.L.E. (12-9-1966) episode "The Abominable Snowman Affair" (“Calamity” Rogers)
Ghostbreakers (1967) (unsold pilot)
Bright Promise (cast member in 1971)
The Delphi Bureau (1972-1973)
Beggarman, Thief (1979) (miniseries)
Falcon Crest (recurring cast member from 1982-1983) played Amanda Croft
Finder of Lost Loves (1984-1985)
General Hospital (cast member from 1984-2004) played Amanda Barrington
A Message from Holly (1992)
Baywatch (recurring cast member from 1993-1998) played Irene Buchannon
Port Charles (cast member from 1999-2003) Played Amanda Barrington
Empire State Building Murders (2008)
Getting On (US) (2013)
Fun for the Money (1941)
Bitter Sweet (1941)
Street Scene (1947)
My Romance (1948)
Kiss Me, Kate (1949)
Three Wishes for Jamie (1952)
Bells Are Ringing (1958)
Destry Rides Again (1960)
Do I Hear a Waltz? (1966)
Pal Joey (1968)
The Desert Song (1968)
Anniversary Waltz (1969)
Song of Norway (1969)
The Most Happy Fella (1970)
The King and I (1974)
High Button Shoes (1978)
A High-Time Salute to Martin and Blane (1991) (benefit concert)