Hopper was born Elda Furry in Hollidaysburg, Pennsylvania, the daughter of Margaret (née Miller; 1856–1941) and David Furry, a butcher, both members of the German Baptist Brethren. Her siblings included Dora, Sherman, Cameron, Edgar, Frank, and Margaret. Her family was of Pennsylvania Dutch (German) descent. The family moved to Altoona when Elda was three.

On May 8, 1913, Hopper married actor and singer DeWolf Hopper in New Jersey. They had one child, william, who later played Paul Drake in the Perry Mason series. They were divorced in 1922.

As Hopper's movie career waned in the mid-1930s, she looked for other sources of income. In 1935 she agreed to write a weekly Hollywood gossip column for the Washington Herald at $50 a week, which was cancelled after four months when she refused to take a $15 pay-cut. In 1937, she was offered another gossip column opportunity, this time with the Los Angeles Times. Her column, entitled "Hedda Hopper's Hollywood", debuted on February 14 (St. Valentine's Day), 1938. Hopper could not type, or spell very well, so she dictated her column to a typist over the phone. Initially facing stiff competition against Louella Parsons, who had a monopoly on Hollywood gossip, Hopper used her extensive contacts forged during her acting days to gather material for her column. Her first major scoop had national implications: in 1939 Hopper printed that President Franklin Roosevelt's son James Roosevelt was divorcing his wife Betsey after being caught in an affair with a nurse at the Mayo Clinic.

Hopper had an acting role in a radio soap opera, playing Portia Brent on the Blue Network's Brenthouse beginning in February 1939. She debuted as host of her own radio program, The Hedda Hopper Show, November 6, 1939. Sponsored by Sunkist, she was heard on CBS three times a week for 15 minutes until October 30, 1942. From October 2, 1944, to September 3, 1945, Armour Treet sponsored a once-a-week program. On September 10, 1945, she moved to ABC, still sponsored by Armour, for a weekly program that continued until June 3, 1946. Hopper moved back to CBS October 5, 1946, with a weekly 15-minute program, This Is Hollywood, sponsored by Procter & Gamble. It ran until June 28, 1947.

Actress Ingrid Bergman was also blacklisted as a result of Hedda Hopper's sustained negative coverage in her columns. Hopper had supported Bergman in her column throughout the 1940s, advocating for her to land starring roles in The Bells of St. Mary's (1945) and Joan of Arc (1948). She was enraged when Bergman lied to her about being pregnant with married Director Roberto Rossellini's baby. Hopper had believed Bergman, printing a fervent denial of the rumor in 1949. However, Bergman was indeed pregnant, and the news was leaked to Hopper's arch-rival Louella Parsons, who got the scoop. Seeking revenge, Hopper launched a PR campaign decrying Bergman for being pregnant out of wedlock and carrying a married man's child.

Charlie Chaplin was another target of Hedda Hopper's vitriol because of his alleged Communist sympathies and his penchant for much younger women, which she considered immoral. She also loathed him for remaining a British citizen and not becoming an American, which she considered an act of ingratitude towards a country which had given him so much. When in 1943 he denied that he was the father of 22-year old Actress Joan Barry's child, Hopper assisted Barry in filing a paternity suit against Chaplin, launching a campaign of attrition against him through her column and calling for him to be deported for his "moral turpitude". She defended her behavior by stating that she wished to make an Example of Chaplin as "a warning to others involved in dubious relationships." Her grudge deepened when, later in the year, Chaplin married 23-year old Oona O'Neill and gave the scoop to Louella Parsons out of spite to Hedda. For years after the paternity trial, Hopper cooperated with the FBI to destabilize Chaplin's career. This involved her printing damaging information leaked by the FBI concerning Chaplin's past Communist affiliations, while Hopper in turn provided the agency with unsavory gossip about Chaplin's personal life gleaned from her informants. Her sustained criticism of Chaplin was one of the factors which contributed to his being denied re-entry to the United States in 1952.

Hopper was one of the driving forces behind the creation of the Hollywood blacklist, using her 35 million strong readership to destroy the careers of those in the entertainment industry whom she suspected of being Communists, having Communist sympathies, being homosexual, or leading dissolute lives. She was a leading member of the Motion Picture Alliance for the Preservation of American Ideals, founded in 1944 and devoted to rooting out suspected Communists in Hollywood. She considered herself to be a guardian of moral standards in Hollywood and bragged that she need only wag her finger at a Producer and he would break off an adulterous affair instantly.

Hopper had several acting roles during the latter part of her career, including brief cameo appearances as herself in the movie Sunset Boulevard (1950) and The Patsy (1964), as well as episodes of The Martha Raye Show, I Love Lucy, The Ford Show, Starring Tennessee Ernie Ford, and The Beverly Hillbillies, starring Buddy Ebsen. Her autobiography, From Under My Hat (Doubleday, 1952) was followed by The Whole Truth and Nothing But (1962), also published by Doubleday. She remained active as a Writer until her death, producing six daily columns and a Sunday column for the Chicago Tribune syndicate, as well as writing articles for Celebrity magazines such as Photoplay.

Hopper strongly supported the House Un-American Activities Committee (HUAC) hearings and was a guest and speaker of the Women's Division at the 1956 Republican National Convention held in San Francisco to renominate the Eisenhower-Nixon ticket.

In 1958, Hopper made racist remarks to African American actor Sidney Poitier. While interviewing him, she asked if he could sing, because "so many of your people do." When he replied that he could not, she said: "You're the first one I've ever met who says he can't sing. I've never known any of your people who couldn't sing."

On January 10, 1960, a television special, Hedda Hopper's Hollywood, aired on NBC. Hosted by Hopper, guest interviews included a remarkably eclectic mix of past, current and Future stars: Lucille Ball (a longtime friend of Hopper), Francis X. Bushman, Liza Minnelli, John Cassavetes, Robert Cummings, Marion Davies (her last public appearance), Walt Disney, Janet Gaynor, Bob Hope, Hope Lange, Anthony Perkins, Debbie Reynolds, James Stewart, and Gloria Swanson.

In 1963, she complained in her column that three out of five Best Actor Oscar nominees were British and only two were American. She added that: "The weather’s so foul on that tight little isle that, to get in out of the rain, they all gather in theatres and practise Hamlet on each other."

Actor Kirk Douglas recounted an interaction between Hopper and Elizabeth Taylor. At the 1965 premiere of Taylor and husband Richard Burton's film The Sandpiper, Hopper began to complain when she saw Screenwriter Dalton Trumbo's screen credit (she had led the charge in blacklisting Trumbo for his Communist party membership). This led Taylor to turn around and say "Hedda, why don't you just shut the f*** up?"

Hopper died on February 1, 1966, of double pneumonia at the age of 80 in Cedars of Lebanon Hospital in Hollywood. She is buried at Rose Hill Cemetery, Altoona, Pennsylvania.

In 1985, Jane Alexander received a Primetime Emmy Award nomination portraying Hopper in the television film Malice in Wonderland, opposite Elizabeth Taylor as Louella Parsons.

In 1995, she was portrayed by Katherine Helmond in Liz: The Elizabeth Taylor Story (1995 TV film)

In 1999, Rue McClanahan played Priscilla Tremaine, a thinly veiled version of Hopper, on the AMC's show The Lot, a comedic limited series about the Golden Age of Hollywood.

In 2002 by Ingrid van Bergen in The Man in the Moon. A Radio-ballett with Charlie Chaplin. A piece for Acoustic Stage Dt. Der Mann im Mond. Ein Radio-Ballett mit Charlie Chaplin. Stück für Akustische Bühne. Written by Evelyn Dörr, on West-German-Broadcasting-Network Cologne in 2002.

In 2006 by Jenn Colella in Chaplin: The Musical, on Broadway in 2012.

In 2015, Helen Mirren played Hedda Hopper in the movie Trumbo directed by Jay Roach.

The New York City Opera announced that it will stage the East Coast premiere of Stewart Wallace's Hopper’s Wife — a 1997 chamber opera about an imagined marriage between Painter Edward Hopper and Hedda Hopper—at Harlem Stage from April 28 through May 1, 2016.

In 2017, in the first season of Feud, Hopper was played by Judy Davis and received a Primetime Emmy Award nomination in the portrayal of the rivalry between Bette Davis and Joan Crawford.