As a teenager, Ball left her Jamestown, New York home to pursue a career in show business, adopting the stage name Diane Belmont. After being fired from several chorus jobs, she retreated to her hometown. Returning to NYC in the early 1930s, Ball was hired as a Hattie Carnegie model but that career was cut short by a bout with what was diagnosed as rheumatoid arthritis. Following two years of intense pain and experimental treatments, she had recovered sufficiently and embarked on a Hollywood career, which at first consisted mostly of walk-ons and bit roles before she was turned into a glamorous Goldwyn showgirl in Eddie Cantor musicals like "Roman Scandals" (1933). Put under contract by Columbia, the statuesque then-blonde actress continued to appear in small roles before her option was dropped. RKO hired Ball at the urging of producer Pandro S. Berman, who featured her in supporting roles in the Astaire-Rogers films, "Roberta", "Top Hat" (both 1935) and "Follow the Fleet" (1936).

Playing alongside Ginger Rogers (whose mother also mentored Ball) and Katharine Hepburn, she won strong notices for her turn as a tough, aspiring actress in "Stage Door" (1937). But the comedic side of Ball began to emerge when she supported the Marx Brothers in "Room Service" and essayed a wacky actress in "The Affairs of Annabel" (1938) and its sequels. She further proved adept at playing jaded sophisticates in the college musicals "Too Many Girls" (1940, with future husband Desi Arnaz) and "Best Foot Forward" (1943) and excelled as a hard-hearted nightclub star in the Damon Runyon melodrama-fable "The Big Street" (1942). Signing with MGM, Ball starred in the film version of the hit Broadway musical "Du Barry Was a Lady" (1943) opposite Red Skelton but the majority of her subsequent vehicles favored her male co-stars. Failing to break-out as a film star, she launched a successful radio career in the late 40s, starring as a dizzy housewife in the CBS comedy "My Favorite Husband" (1947-51). That success led to slightly improved studio vehicles (e.g., "The Fuller Brush Girl" 1950) and two fine comedies opposite Bob Hope, "Fancy Pants" (1949) and "Sorrowful Jones" (1950). By this point in her career, she had also adopted her trademarked hennaed hair.

Perhaps sensing that her film career was stalled, Ball turned to the fledgling medium of television. Asked to recreate her radio persona in a comedy series, the actress pushed to have the Cuban-born Arnaz as her co-star. CBS executives balked at the idea claiming that audiences would not accept them as a married couple. To assuage those concerns, Ball and Arnaz embarked on a successful vaudeville tour that proved not only that audiences would embrace them as a couple but also that they could work together and not seriously compromise their marriage. "I Love Lucy" (CBS, 1951-57) was an almost instant hit. Filming with the then-unique three camera technique in front of a studio audience, the show defined the prototype for the situation comedy, focusing on the antics of a married couple and their neighbors (which was "imitated" by such other classics as "The Honeymooners" and "All in the Family", to name just two). From the series' debut in October 1951, Ball emerged a full-fledged star with viewers tuning in weekly to laugh at her zany antics and well-meaning schemes which utilized every aspect of her talents. Her Lucy Ricardo could engage in dexterous physical comedy or in absurd disguises but still emerge with her dignity and her lady-like persona in tact. When Ball became pregnant, it was incorporated into the show and, shrewd businesswoman that she was, she even planned the cesarean birth of her own son to coincide with the TV birth.

After nearly six years, Ball and Arnaz ended the series in favor of a series of one-hour comedy specials featuring the characters of "I Love Lucy" that aired originally as part of "Desilu Playhouse" and were later packaged as "The Lucille Ball-Desi Arnaz Show/The Lucy-Desi Comedy Hour". Having wisely retained all the rights to "I Love Lucy" after its initial broadcast, the couple racked up enormous profits from the sale of its syndication rights, an unheard of event in the early 50s. Eventually, Arnaz and Ball sold the filmed episodes back to CBS for a tidy profit and the show continues to air somewhere in the world to this day.

In 1960, Arnaz and Ball divorced and she attempted to re-establish herself in other venues. Ball headlined the musical "Wildcat" (1960) which proved too grueling and she withdrew for health reasons. She fared slightly better in a big screen reteaming with Bob Hope in "The Facts of Life". After assuming the position as head of Desilu Productions, Ball was in the enviable position as one of the most powerful women in Hollywood, heading a major production company. (She bought out Arnaz's share in 1962 and five years later sold the company to Gulf + Western for a tidy profit.) Not content to be just a mogul, she mustered a stock company of featured players (including Vivian Vance, Gale Gordon and Mary Jane Croft) and went on to success as the star of two long-running CBS sitcoms "The Lucy Show" (CBS, 1962-68) and "Here's Lucy" (CBS, 1968-74). Disgruntled with CBS and with the kinds of issue-oriented sitcoms proliferating during the 70s, Ball signed a deal with rival network NBC and in 1980 made a 90-minute special, which included a pilot in which Donald O'Connor starred alongside a banjo-playing teen-ager. Although Ball proclaimed at the end of the special "That's what I call entertainment!" the network and sponsors did not. Ball's influence in TV had waned. But she did not remain entirely idle.

Having enjoyed success on the big screen reteaming with Henry Fonda in the comedy about a blended family "Yours, Mine and Ours" (1968), Ball sought out additional roles. She and her second husband, former comic Gary Morton, purchased the rights to the 1966 stage musical "Mame". Despite the objections of composer Jerry Herman and those who wanted Angela Lansbury to recreate her Broadway triumph, Ball undertook the role to a less than warm critical reception. As she had just recuperated from a broken leg, her dancing was limited and often shot from the waist up. Ball also reportedly battled on the set with Beatrice Arthur (recreating her Tony-winning stage role as Vera Charles) and had Madeline Kahn replaced with the decidedly older (and frumpier) Jane Connell (playing Agnes Gooch). The result was a creative and financial failure. Ball would never make another film, although her production company was involved with "All the Right Moves" (1983), one of Tom Cruise's early hits.

Undaunted by the "Mame" debacle, Ball undertook a dramatic role as a homeless woman in the TV-movie "The Stone Pillow" (CBS, 1985). Her fans reacted with horror and the critics were divided over her performance. Many could not get past her larger-than-life TV personality and could only see the comic "Lucy" rather than an actress. Deciding to give series TV another whirl, Ball portrayed a free-spirited grandmother, "Life With Lucy" (1986), was produced with Aaron Spelling and had a 22-episode guaranteed order from ABC. But it flopped almost immediately and was off the air within weeks with some filmed episodes never shown. For the remainder of her life, Ball confined her TV appearances to an occasional awards special or interview. Years after her 1989 death, the manuscript for a long-lost autobiography was found in a filing cabinet. Covering her life into the 60s, "Love, Lucy" became an instant bestseller when it was published in 1996.