In 1938, Matthews was named "Miss Chicago" and, in doing so, qualified for a trip to California and a screen test. While in California, she auditioned for the Earl Carroll Follies and won a role in the show for 1939.

In 1939, Mathews had some bit parts in films, using the name Jeanne Francis. In 1942, she conducted a screen test for Samuel Goldwyn of MGM Studios. That same night, she married radio Writer John Arthur Stockton in Tijuana, Mexico, the scion of a wealthy Chicago family. Goldwyn immediately canceled her contract. In late January 1944, she had the marriage annulled, and she never remarried, though she was associated with several other men, including a considerably younger Don Durant, two years before he was cast in his own CBS Western series, Johnny Ringo, according to a report from Walter Winchell.

Mathews appeared on Broadway as Karen Jackson in With a Silk Thread (1950).

One of her first television guest-starring roles was as Miss Jennings in the 1951 episode "The Slocum Family" and Anne Hardy in "Blacksmith Story" (1952) of the syndicated Western series, The Adventures of Wild Bill Hickok, starring Guy Madison and Andy Devine. The Anne Hardy role was used in 1954 in the film The Two Gun Teacher. She also played Alice Miller in the 1952 episode "Big Trap" of Racket Squad. That same year, she appeared twice in another syndicated Western series, The Cisco Kid.

She was known for her roles in the film Swamp Women (1955), one of the first pictures directed by Roger Corman and also starring Beverly Garland and Mike Connors. Mathews was also cast in Treasure of Ruby Hills (1955) and Betrayed Women (1956). Even during the late 1930s, when she will still in her teens, she was appearing in uncredited roles in various films.

Other Mathews roles were on three CBS Western series: as Dellie Hartford in "The General's Disgrace" (1957) on The Adventures of Jim Bowie, as Millie Gwyn in "The Farrand Story" (1958) on Trackdown, and as Libby on "This Man Must Die" (1958) on Dick Powell's Zane Grey Theatre. She appeared in two episodes of Alfred Hitchcock Presents.

Mathews played Lola in the 1958 episode "The Pickpocket" of the NBC Western series Tales of Wells Fargo, starring Dale Robertson. She had appeared with Robertson five years earlier in the film City of Bad Men. In 1958, she was cast as Jill Crane in the film Showdown at Boot Hill and as Bess Corbin in "No Tears for the Dead" on the television series The Texan.

On January 9, 1959, she played Mrs. Elaine Lamson in the episode "Not an Enemy in the World" on 77 Sunset Strip. Around this time, she was cast on two episodes of Perry Mason. Other 1959 roles were as Jan Van Pelt in "The Glass Diamond" of Markham and as Rita Kirk in "No Laughing Matter" in the last season of Richard Diamond, Private Detective. She appeared twice in 1959 on M Squad, starring Lee Marvin.

In 1960, Mathews was cast as Phyllis Brady in "Babs Meets Phyllis Brady", an episode of the ABC sitcom, Guestward, Ho!, set on a dude ranch in New Mexico. Mathews played the Western bandit Belle Starr in "A Bullet for the D.A", a 1961 episode of the syndicated western anthology series, Death Valley Days.

Her last television roles were on the CBS sitcom, Pete and Gladys (1962), Rawhide (1964) in the episode 'Incident of the Odyssey', and Ben Casey (1966). Twelve years later in 1978, she was cast as a woman in a restaurant in her final acting role on the television movie, Fame, about a waiter who becomes an overnight success as a Playwright.

From 1971-86, Mathews operated Mathews Travel Center in Sherman Oaks in the San Fernando Valley of California. In March 1977, Mathews took over the Hidden Valley Ranch in nearby Reseda, California, where she raised pygmy goats, rabbits, chickens, Muscovy ducks, and worms. She also produced audio/visual travelogues and television dramas. In 1982, she was cited for her success in raising miniature horses.