Rooney was born Joseph Yule, Jr. on September 23, 1920, in Brooklyn, New York, the only child of vaudevillians Nellie W. Carter, from Kansas City, Missouri and Joe Yule, a native of Glasgow, Scotland. His mother was a former chorus girl and a burlesque performer. When Rooney was born, his parents were appearing in a Brooklyn production of A Gaiety Girl. Rooney later recounted in his memoirs that he began performing at the age of 17 months as part of his parents' routine, wearing a specially tailored tuxedo.

Rooney's parents separated when he was four years old in 1924, and he and his mother moved to Hollywood the following year. His made his first film appearance at age six in 1926, in the short Not to be Trusted. Rooney got bit parts in films such as The Beast of the City (1932) and The Life of Jimmy Dolan (1933), which allowed him to work alongside stars such as Joel McCrea, Colleen Moore, Clark Gable, Douglas Fairbanks, Jr., John Wayne and Jean Harlow. He enrolled in the Hollywood Professional School and later attended Hollywood High School, graduating in 1938.

Rooney was one of the last surviving actors of the silent picture era. His movie career spanned 88 years, from 1926 to 2014, continuing until shortly before his death. During his peak years from the late 1930s to the early 1940s, Rooney was among the top box-office stars in the United States.

His mother saw an advertisement for a child to play the role of "Mickey McGuire" in a series of short films. Rooney got the role and became "Mickey" for 78 of the comedies, running from 1927 to 1936, starting with Mickey's Circus (1927), his first starring role.

At the height of a career that was marked by precipitous declines and raging comebacks, Rooney performed the role of Andy Hardy in a series of 15 films in the 1930s and 1940s that epitomized American family values. A versatile performer, he became a celebrated character actor later in his career. Laurence Olivier once said he considered Rooney "the best there has ever been." Clarence Brown, who directed him in two of his earliest dramatic roles, National Velvet and The Human Comedy, said he was "the closest thing to a genius I ever worked with."

He made other films in his adolescence, including several more of the McGuire films. At age 15 he played the role of Puck in the Warner Brothers all-star adaptation of A Midsummer Night's Dream in 1935. Rooney then moved to MGM, where he befriended Judy Garland, with whom he began making a series of musicals that propelled both of them to stardom.

In 1937, Rooney received top billing as Shockey Carter in Hoosier Schoolboy but his breakthrough-role as a dramatic actor came in 1938's Boys Town opposite Spencer Tracy as Father Flanagan, who runs a home for wayward and homeless boys. Rooney was awarded a special Juvenile Academy Award in 1939, for "significant contribution in bringing to the screen the spirit and personification of youth." Wayne describes one of the "most famous scenes" in the film, where tough young Rooney is playing poker with a cigarette in his mouth, his hat is cocked and his feet are up on the table. "Tracy grabs him by the lapels, throws the cigarette away and pushes him into a chair. 'That's better,' he tells Mickey." Louis B. Mayer said Boys Town was his favorite film during his years at MGM.

He made forty-three pictures between the age of 15 and 25. Among those, his role as Andy Hardy became one of "Hollywood's best-loved characters," with Marlon Brando calling him "the best actor in films." For his acting the part in fifteen Andy Hardy films, he received an honorary Oscar in 1938 for "bringing to the screen the spirit and personification of youth" and for "setting a high standard of ability and achievement."

The popularity of his films made Rooney the biggest box-office draw in 1939, 1940 and 1941. For their roles in Boys Town, Rooney and Tracy won first and second place in the Motion Picture Herald 1940 National Poll of Exhibitors, based on the box office appeal of 200 players. Boys' Life magazine wrote, "Congratulations to Messrs. Rooney and Tracy! Also to Metro-Goldwyn-Mayer we extend a hearty thanks for their very considerable part in this outstanding achievement." Actor Laurence Olivier once called Rooney "the greatest actor of them all."

By the end of the 1940s, Rooney's movie characters were no longer in demand and his career went downhill. "In 1938," he said, "I starred in eight pictures. In 1948 and 1949 together, I starred in only three." However, film Historian Jeanine Basinger notes that although his career "reached the heights and plunged to the depths, Rooney kept on working and growing, the mark of a professional." Some of the films which reinvigorated his popularity, were Requiem for a Heavyweight (1962), It's a Mad, Mad, Mad, Mad World (1963) and The Black Stallion (1979). In the early 1980s, he returned to Broadway in Sugar Babies, and "found himself once more back on top."

Rooney was married eight times, with six of the marriages ending in divorce. In 1942, he married his first wife, Actress Ava Gardner, who at that time was still an obscure teenage starlet. They divorced the following year, partly because he had apparently been unfaithful. While stationed in the military in Alabama in 1944, Rooney met and married Betty Jane Phillips, who later became a singer under the name B.J. Baker. They had two sons together. This marriage ended in divorce after he returned from Europe at the end of World War II. His marriage to Actress Martha Vickers in 1949 produced one son but ended in divorce in 1951. He married Actress Elaine Mahnken in 1952 and they divorced in 1958.

Clarence Brown, who directed Rooney in his Oscar-nominated performance in The Human Comedy (1943) and again in National Velvet (1944), enjoyed working with Rooney in films:

In June 1944, Rooney was inducted into the United States Army, where he served more than 21 months (until shortly after the end of World War II) entertaining the troops in America and Europe in Special Services. He spent part of the time as a radio personality on the American Forces Network and was awarded the Bronze Star Medal for entertaining troops in combat zones. In addition to the Bronze Star Medal, Rooney also received the Army Good Conduct Medal, American Campaign Medal, European-African-Middle Eastern Campaign Medal, and World War II Victory Medal, for his military Service.

Rooney's career slumped after his return to civilian life. He was now an adult with a height of only 5 feet 2 inches (1.57 m) and he could no longer play the role of a teenager, but he also lacked the stature of most leading men. He appeared in a number of films, including Words and Music in 1948, which paired him for the last time with Garland on film (he appeared with her on one episode as a guest on The Judy Garland Show. He briefly starred in a CBS radio series, Shorty Bell, in the summer of 1948, and reprised his role as "Andy Hardy", with most of the original cast, in a syndicated radio version of The Hardy Family in 1949 and 1950 (repeated on Mutual during 1952).

In 1949 Variety reported that Rooney had renegotiated his deal with MGM. He agreed to make one film a year for them for five years at $25,000 a movie (his fee until then had been $100,000 but Rooney wanted to enter independent production.) Rooney claimed he was unhappy with the billing MGM gave him for Words and Music.

His first television series, The Mickey Rooney Show: Hey, Mulligan (created by Blake Edwards with Rooney as his own producer), appeared on NBC television for 32 episodes between August 28, 1954, and June 4, 1955. In 1951, he made his directorial debut with My True Story, starring Helen Walker. Rooney also starred as a ragingly egomaniacal television Comedian, loosely based on Red Buttons, in the live 90-minute television drama The Comedian, in the Playhouse 90 series on the evening of Valentine's Day in 1957, and as himself in a revue called The Musical Revue of 1959 based on the 1929 film The Hollywood Revue of 1929, which was edited into a film in 1960.

In 1958, Rooney married Barbara Ann Thomason, but she was murdered by her secret lover in 1966. He then married Barbara's best friend, Marge Lane. That marriage lasted 100 days. He was married to Carolyn Hockett from 1969 to 1975. In 1978, Rooney married his eighth and final wife, Jan Chamberlin. Their marriage lasted until his death, a total of 34 years (longer than his seven previous unions combined), although they separated in 2012.

On February 8, 1960, Rooney was initiated into the Hollywood Walk of Fame with a star heralding his work in motion pictures, located at 1718 Vine Street, one for his television career located at 6541 Hollywood Boulevard, and a third dedicated to his work in radio, located at 6372 Hollywood Boulevard. On March 29, 1984, he received a fourth star, this one for his live performances, located at 6211 Hollywood Boulevard.

In 1961, he guest-starred in the 13-week James Franciscus adventure–drama CBS television series The Investigators. In 1962, he was cast as himself in the episode "The Top Banana" of the CBS sitcom, Pete and Gladys, starring Harry Morgan and Cara Williams.

At his death, Vanity Fair called him "the original Hollywood train wreck." He struggled with alcohol and pill addiction. Ava Gardner was his first wife, and he would go on to marry an additional seven times. Despite earning millions during his career, he had to file for bankruptcy in 1962 due to mismanagement of his finances. Shortly before his death in 2014 at age 93, he alleged mistreatment by some family members and testified before Congress about what he alleged was physical abuse and exploitation by family members. By the end of his life, his millions in earnings had dwindled to an estate that was valued at only $18,000. He died owing medical bills and back taxes, and contributions were solicited from the public.

In 1963, he entered CBS's The Twilight Zone, giving a one-man performance in the episode "The Last Night of a Jockey" (1963). Also in 1963, in 'The Hunt' for Suspense Theater, he played the sadistic sheriff hunting the young Surfer played by James Caan. In 1964, he launched another half-hour sitcom, Mickey. The story line had "Mickey" operating a resort hotel in southern California. His own son Tim Rooney appeared as his character's teenage son on this program, and Emmaline Henry starred as Rooney's wife. The program lasted for 17 episodes.

In addition to his movie roles, Rooney made numerous guest-starring roles as a television character actor for nearly six decades, beginning with an episode of Celanese Theatre. The part led to other roles on such television series as Schlitz Playhouse, Playhouse 90, Producers' Showcase, Alcoa Theatre, The Soldiers, Wagon Train, General Electric Theater, Hennesey, The Dick Powell Theatre, Arrest and Trial (1964), Burke's Law (1963), Combat! (1964), The Fugitive, Bob Hope Presents the Chrysler Theatre, The Jean Arthur Show (1966), The Name of the Game (1970), Dan August (1970), Night Gallery (1970), The Love Boat, Kung Fu: The Legend Continues (1995), Murder, She Wrote (1992), The Golden Girls (1988) among many others.

In 1966, Rooney was working on the film Ambush Bay in the Philippines when his wife Barbara Ann Thomason— a former model and aspiring Actress who had won 17 straight beauty contests in Southern California—was found dead in her bed. Her lover, Milos Milos—who was one of Rooney's actor-friends—was found dead beside her. Detectives ruled it a murder-suicide, which was committed with Rooney's own gun.

Rooney did voice acting from time to time. He provided the voice of Santa Claus in four stop-motion animated Christmas TV specials: Santa Claus Is Comin' to Town (1970), The Year Without a Santa Claus (1974), Rudolph and Frosty's Christmas in July (1979) and A Miser Brothers' Christmas (2008). In 1995, he appeared as himself on The Simpsons episode "Radioactive Man".

A major turning point came in 1979, when Rooney made his Broadway debut in the acclaimed stage play Sugar Babies, a musical revue tribute to the burlesque era costarring former MGM dancing star Ann Miller. Al Jean Harmetz noted that "Mr. Rooney fought over every skit and argued over every song and almost always got things done his way. The show opened on Broadway on October 8, 1979, to rave reviews, and this time he did not throw success away. and Rooney and Miller performed the show 1,208 times in New York and then toured with it for five years, including eight months in London. Co-star Miller recalls that Rooney "never missed a performance or a chance to ad-lib or read the lines the same way twice, if he even stuck to the script." Biographer Alvin Marill states that "at 59, Mickey Rooney was reincarnated as a baggy-pants comedian—back as a top Banana in show biz in his belated Broadway debut."

Rooney garnered a Golden Globe and an Emmy Award for Outstanding Lead Actor in a Limited Series or a Special for his role in 1981's Bill. Playing opposite Dennis Quaid, Rooney's character was a mentally handicapped man attempting to live on his own after leaving an institution. His acting quality in the film has been favorably compared to other actors who took on similar roles, including Sean Penn, Dustin Hoffman and Tom Hanks. He reprised his role in 1983's Bill: On His Own, earning an Emmy nomination for the turn.

In 1983, the Academy of Motion Picture Arts and Sciences gave Rooney their Academy Honorary Award for his lifetime of achievement.

He toured Canada in a dinner theatre production of The Mind with the Naughty Man in the mid-1990s. He played The Wizard in a stage production of The Wizard of Oz with Eartha Kitt at Madison Square Garden. Kitt was later replaced by Jo Anne Worley.

Rooney wrote a memoir titled Life is Too Short, published by Villard Books in 1991. A Library Journal review said that "From title to the last line, 'I'll have a short bier', Rooney's self-deprecating humor powers this book." He wrote a novel about a child star, published in 1994, The Search For Sunny Skies.

In 1996, a Golden Palm Star on the Palm Springs Walk of Stars was dedicated to Rooney.

In 1997, Rooney was arrested on suspicion of beating his wife, but charges were dropped due to lack of evidence.

Rooney had been addicted to sleeping pills; he overcame the sleeping pill addiction in 2000, when he was in his late 70s.

Rooney appeared in television commercials for Garden State Life Insurance Company in 2002.

Rooney and his wife Jan toured the country in 2005 through 2011 in a musical revue called Let's Put on a Show. Vanity Fair called it "a homespun affair full of dog-eared jokes" that featured Rooney singing George Gershwin songs.

In 2006, Rooney played Gus in Night at the Museum. He returned to play the role again in the sequel Night at the Museum: Battle of the Smithsonian in 2009, in a scene that was deleted from the final film.

On May 26, 2007, he was grand marshal at the Garden Grove Strawberry Festival. Rooney made his British pantomime debut, playing Baron Hardup in Cinderella, at the Sunderland Empire Theatre over the 2007 Christmas period, a role he reprised at Bristol Hippodrome in 2008 and at the Milton Keynes theatre in 2009.

In April 2011, the temporary restraining order that Rooney was previously granted was replaced by a confidential settlement between Rooney and his stepson, Aber. Christopher Aber and Jan Rooney denied all the allegations.

At the time of his death, he was married to Jan Chamberlin Rooney, although they had separated in June 2012. He had nine children and two stepchildren, as well as 19 grandchildren and several great-grandchildren.

In May 2013, Rooney sold his home of many years, reportedly for $1.3 million, and split the proceeds with his wife, Jan.

Rooney died on April 6, 2014, of natural causes in Los Angeles at the age of 93.

An October 2015 article in The Hollywood Reporter maintained that Rooney was frequently abused and financially depleted by his closest relatives in the last years of his life. The article said that it was clear that "one of the biggest stars of all time, who remained aloft longer than anyone in Hollywood history, was in the end brought down by those closest to him. He died humiliated and betrayed, nearly broke and often broken." Rooney suffered from bipolar disorder and had attempted suicide two or three times over the years, with resulting hospitalizations reported as "nervous breakdowns".