Born in Barstow, California to George A. Crain (a school teacher) and Loretta Carr, she moved to Los Angeles as a young child. An excellent ice skater, Crain first attracted attention when she was crowned Miss Pan Pacific at L.A.'s Pan Pacific Auditorium. Later, while still in high school, she was asked to make a screen test opposite Orson Welles. She did not get the part, but in 1943, at the age of 18, she appeared in a bit part in the movie The Gang's All Here.

In 1944 she starred in Home in Indiana, and In the Meantime, Darling. Her acting was critically panned, but she rebounded in the hit Winged Victory. During World War II, Crain's fan mail was second in volume only to that of Betty Grable.

In 1945 she starred in State Fair, and in 1949 in three films,A Letter to Three Wives, The Fan and Pinky, for which she was nominated for the Academy Award for Best Actress. Pinky was a controversial movie, since it told the story of a girl who passes for white in the northern United States. Although Lena Horne and other black actresses were considered for the role, Darryl F. Zanuck chose to cast a white actress for box-office reasons.

In 1950, Crain starred opposite Myrna Loy and Clifton Webb in Cheaper by the Dozen. Next, Crain paired up with Cary Grant, for the Joseph L. Mankiewicz production of People Will Talk (1951) . 1952 saw Crain again teamed with Loy in the release of Belles on Their Toes, the sequel to Cheaper by the Dozen. While still at Fox, Crain gave an excellent performance as a young wife quickly losing her mind amidst high seas intrigue in Dangerous Crossing, co-starring Michael Rennie. Crain then starred in a string of pictures for Universal, including notable pairings with Kirk Douglas, such as Man Without a Star (1955).

Also in 1955, Crain also showed off her lively dancing abilities in Gentlemen Marry Brunettes, co-starring Jane Russell, Alan Young, and Rudy Vallee. The production was filmed on location in Paris and Crain's singing in the film was dubbed, as was customary. The film was based on the Anita Loos novel that was a sequel to her acclaimed Gentlemen Prefer Blondes. Gentlemen Marry Brunettes was popular throughout Europe at the time and was released in France as A Paris Pour les Quatre ("Paris For The Four"), and in Belgium as Cevieren Te Parijs. Later in the 50's, Crain, Russell, and another actress teamed up for a short-lived singing and dancing lounge act at one of the hotels on the Las Vegas Strip.

In 1956, Crain starred opposite Glenn Ford, Russ Tamblyn, and Broderick Crawford in the compelling Western, Fastest Gun Alive. The film was directed by Russell Rouse. In 1957, she was a socialite who helps a crushed singer (played by Frank Sinatra) redeem himself in The Joker Is Wild.

In 1959, Crain appeared in a prestigious CBS Television Special production of "Meet Me in St. Louis." Also starring in the broadcast were Myrna Loy, Walter Pidgeon, Jane Powell, and Ed Wynn. A sign of the times: top-billing on the program went to co-star Tab Hunter!

Film roles became fewer in the 1960s as Crain went into semi-retirement. Crain was captivating as Nefertiti in the 1961 Italian production of Queen of the Nile, with Edmund Purdom and Vincent Price. During this period Crain did a stint as one of the What's My Line? Mystery Guests on the popular Sunday night CBS-TV program . Crain's last film role was in Skyjacked in 1972.

Against her mother's wishes, Crain married former RKO Studios contract player Paul Brinkman on December 31, 1946; the first of their 7 children was born the following April. During the early 1950s, Crain was earning approx. $3,500 per week. Crain and her husband Brinkman bought a large, lovely home for their growing family on Roxbury Drive in Beverly Hills. (The home can be seen and is described by Bette Davis in candid footage of a driving sequence in the 1952 now cult-classic, The Star.) The marriage was rocky for some years. Crain obtained an interlocutory divorce decree, each spouse claiming the other had been unfaithful (she also claimed Brinkman had been abusive), but the couple reconciled on the eve of their 11th wedding anniversary.

As a lifelong devout Catholic, Jeanne Crain Brinkman and her husband Paul remained married, though they lived separately in Santa Barbara, California, until Mr. Brinkman's death in October of 2003. Crain passed away a few months later and it was speculated that she died of a broken heart. Crain's funeral Mass was held at the Old Santa Barbara Mission. Crain is buried in the Brinkman family plot at Santa Barbara Cemetery. The couple outlived two of their children. The Brinkmans were survived by five adult children, including Paul Brinkman Jr., a successful television executive, most known for his work on CBS TV's JAG. Crain was also survived by many grandchildren, nieces, and nephews.

Crain's career is fully documented by an extraordinary collection of memorabilia about her assembled by the late Charles J. Finlay (longtime publicist at 20th Century Fox). The Jeanne Crain collection resides perpetually at the Wesleyan University Cinema Archives in Middletown, Connecticut. These archives also hold the papers of Frank Capra, Ingrid Bergman, Clint Eastwood, and others.