Over the next decade, Dru appeared frequently in films and on television. She was cast often in western films such as Howard Hawks's Red River (1948), and John Ford's She Wore a Yellow Ribbon (1949), and Wagon Master (1950).

She gave a well-received performance in the dramatic film All the King's Men (1949) and co-starred with Dan Dailey in The Pride of St. Louis (1952) about major-league baseball pitcher Jerome "Dizzy" Dean.

She appeared in the James Stewart drama Thunder Bay in 1953 and then a Martin and Lewis comedy 3 Ring Circus (1954). Her film career petered out by the end of the 1950s, but she continued working frequently in television, most notably as "Babs Wooten" on the 1960-61 sitcom, Guestward, Ho!.

After Guestward, Ho!, she appeared sporadically for the rest of the 1960s and the first half of the 1970s, with one feature film appearance, in Sylvia (1965), and eight television appearances.

For her contribution to the television industries, Dru was awarded a star on the Hollywood Walk of Fame.

She was the elder sister of Peter Marshall, an actor and singer best-known as the original host of the American game show Hollywood Squares.

Before moving to Hollywood, Dru met and married popular singer Dick Haymes. Joanne Dru had three children by her first marriage; Richard Ralph Haymes (born July 24, 1942), Helen Joanna Haymes (born May 13, 1944), Barbara Nugent Haymes (born September 19, 1947).

She was divorced from Haymes in 1949, then married John Ireland, who was also in Red River, less than a month later. Dru and Ireland were divorced in 1957. She had no children from her subsequent three marriages.

She died in Los Angeles, California in 1996, aged 74, from lymphedema.