Due to her insistence, Jean Peters was given the title role in Anne of the Indies (1951), which the press declared was the film that finally brought her stardom. Before its release, she was cast in Viva Zapata! (1952) opposite Marlon Brando. Julie Harris had been considered for this role. Also in 1951, Peters had her first collaboration with Marilyn Monroe, when they had secondary roles in As Young as You Feel. Peters was set to play the title role in the drama film Wait Till the Sun Shines, Nellie (1952). It was the first time since the beginning of her career that Peters received this much publicity. While shooting the film in Hutchinson, Kansas, Peters was honored with the title ‘Miss Wheatheart of America’. In 1953 the director Samuel Fuller chose Peters over Marilyn Monroe for the part of Candy in Pickup on South Street. He said he thought Peters had the right blend of sex appeal and the tough-talking, streetwise quality he was seeking. Monroe, he said, was too innocent looking for the role. Shelley Winters and Betty Grable had previously been considered but both had turned it down. Because of the sex symbol status of her character, Peters was not thrilled with the role. She preferred playing more down-to-earth, unglamorous parts as she had done with Anne of the Indies (1951), Viva Zapata! (1952) and Lure of the Wilderness (1952). For Pickup on South Street, Jean Peters was advised to bleach her hair but she refused to do so. She wanted to avoid comparisons with Winters and Grable. She did agree to adopt a “sexy shuffle” for the role. She was helped by Marilyn Monroe to understand the role of a siren. Peters later said that she had enjoyed making the film, but announced in an interview that she was not willing to take on other siren roles. She said: “‘[Pickup on South Street]’ was fine for my career, but that doesn’t mean I’m going to put on a tight sweater and skirt and slither around. I’m just not the type. On Marilyn Monroe it looks good. On me it would look silly.” In another interview, Peters explained that playing down-to-earth and sometimes unwashed women have the most to offer in the way of drama.

Jean Peters and Marilyn Monroe starred together in another 1953 film noir, Niagara, also starring Joseph Cotten. In Niagara, Peters replaced Anne Baxter, with whom she co-starred in the anthology film O. Henry’s Full House (1952). Shooting of Niagara took place in the summer of 1952. Peters’ character was initially the leading role, but the film eventually became a vehicle for Monroe, who was by that time more successful. Peters’ third film in 1953, A Blueprint for Murder, reunited her with Joseph Cotten. She was assigned to the film in December 1952 and told the press she liked playing in the film because it allowed her to sing, but there is no song by her in the picture, only the playing of a piano. Shortly after the film’s premiere in July 1953, the studio renewed Peters’ contract for another two years. In 1953 she also starred in the film noir Vicki. The writer Leo Townsend bought the story of the film, a remake of I Wake Up Screaming, as a vehicle for Peters. Townsend said that he gave the role to Peters in December 1952, because she was “one of the greatest sirens he’s ever seen.” Next, Peters was assigned to replace Crain in the film Three Coins in the Fountain (1954), which was shot on location in late 1953 in Italy. Peters was unsatisfied with her role and said in a September 1953 interview: “When I heard Dorothy McGuire, Clifton Webb and Maggie McNamara were going to be in the picture, I thought I would finally have the kind of role that suited me. They sounded like smart, sophisticated company. But when I got to Italy and read the script, I discovered I was going to be an earthy kind of girl again. The script had me nearly being killed in a runaway truck.” However, the film became a great success and brought Peters again into the limelight.

Other 1954 films co-starring Jean Peters were the westerns Apache and Broken Lance. Although Broken Lance did not attract much attention, she was critically acclaimed for her performance in Apache. One critic praised her for “giving an excellent account for herself”, declaring she was “on her way to becoming one of the finest young actresses around Hollywood today.” Peters’ next (and ultimately final) film was A Man Called Peter (1955), in which she played Catherine Marshall, the wife of Peter Marshall, a Presbyterian minister and Chaplain of the United States Senate. After the release of A Man Called Peter, Peters refused several roles, for which she was placed on suspension by the studio. Deciding she had had enough, Peters left Fox to focus on her private life. Following her marriage to Howard Hughes, she retired from acting. In 1957, the producer Jerry Wald tried to persuade her not to leave Hollywood but had no luck. She was supposedly discouraged from continuing as an actress by Hughes, and reported in late 1957 that she was planning on becoming a producer. In March 1959, it was announced that Peters was to return to the screen for a supporting role in The Best of Everything. But, she did not appear in that film; and, despite her earlier announcement, never produced a film.

In 1970, rumors arose of Jean Peters making a comeback to acting when the press reported that she was considering three film offers and a weekly TV series for the 1970–1971 season. She chose the television movie Winesburg, Ohio (1973). Afterward, she said, “I am not pleased with the show or my performance in it. I found it rather dull.” At the beginning, she had expressed enthusiasm for the project, saying: “I’m very fond of this script. It’s the right age for me. I won’t have to pretend I’m a glamour girl.” Her co-star William Windom praised her, saying she was “warm, friendly and charming on the set.” In 1976, Peters had a supporting role in the TV miniseries The Moneychangers. When asked why she took the role, she said: “I’ll be darned if I know. A moment of madness, I think. I ran into my old friend Ross Hunter, who was producing The Moneychangers for NBC-TV, and he asked me if I wanted to be in it. It seemed like fun. It’s a nice part – not too big – and I greatly admire Christopher Plummer, whom I play opposite.” Peters appeared in the 1981 television film Peter and Paul, produced by her husband. She guest starred in Murder, She Wrote in 1988, which was her final acting performance. Jean Peters died of leukemia in 2000 in Carlsbad, California, two days before her 74th birthday. She was buried at the Holy Cross Cemetery in Culver City, California.