Instrumental to the sisters' success over the years were their parents, Olga and Peter, their orchestra leader and musical arranger, Vic Schoen (1916–2000), and Jack and David Kapp, who founded Decca Records.

When the sisters burst upon the music scene in the late 1930s, they shook a very solid musical foundation, producing a slick harmonic blend by singing at the top of their lungs while trying—successfully—to emulate the blare of three harmonizing trumpets, with a full big band racing behind them. Some bandleaders of the day, such as Artie Shaw, along with his Musicians, resented them for taking the focus away from the band and emphasizing the vocals instead. They were in as high demand as the big bandleaders themselves, many of whom did not want to share the spotlight and play backup to a girl trio.

The Andrews Sisters were the most sought-after Singers in theater shows worldwide during the 1940s and early 1950s, always topping previous house averages. The trio headlined at the London Palladium in 1948 and 1951. They hosted their own radio shows for ABC and CBS from 1944 to 1951, singing specially written commercial jingles for such products as Wrigley's chewing gum, Dole pineapples, Nash motor cars, Kelvinator home appliances, Campbell's soups, and Franco-American food products. The western-themed "The Andrews Sisters' Show" (subtitled "Eight-to-the-Bar Ranch"), co-hosted by Gabby Hayes, began in 1944 and featured a special guest every week.

Buck Privates, with Abbott and Costello, featured the Andrews Sisters' best-known song, "Boogie Woogie Bugle Boy." This Don Raye-Hughie Prince composition was nominated for Best Song at the 1941 Academy Awards ceremony.

The Andrews Sisters sing the title song as the opening credits roll and also perform two specialty numbers in the all-star revue Hollywood Canteen (1944). They can be seen singing "You Don't Have to Know the Language" with Bing Crosby in Paramount's Road to Rio with Bob Hope, that year's highest-grossing movie. Their singing voices are heard in two full-length Walt Disney features: "Make Mine Music" in a segment which featured animated characters Johnny Fedora and Alice Blue Bonnet; and "Melody Time", in the segment Little Toot, both of which are available on DVD today).

Nevertheless, they found instant appeal with teenagers and young adults who were engrossed in the swing and jazz idioms, especially when they performed with nearly all of the major big bands, including those led by Glenn Miller, Benny Goodman, Buddy Rich, Tommy Dorsey, Jimmy Dorsey, Gene Krupa, Joe Venuti, Freddie Slack, Eddie Heywood, Bob Crosby (Bing's brother), Desi Arnaz, Guy Lombardo, Les Brown, Bunny Berigan, Xavier Cugat, Paul Whiteman, Ted Lewis, Nelson Riddle and mood-master Gordon Jenkins, whose orchestra and chorus accompanied them on such successful soft and melancholy renditions as "I Can Dream, Can't I?" (which shot to number one on Billboard and remained in the Top 10 for 25 weeks), "I Wanna Be Loved", "There Will Never Be Another You", and the inspirational "The Three Bells", which was an English version of the French 1946 rendition by Édith Piaf & Les Compagnons de la chanson; along with several solo recordings with Patty, including a cover version of Nat King Cole's "Too Young", "It Never Entered My Mind", "If You Go" and "That's How A Love Song Is Born".

While the sisters specialized in swing, boogie-woogie, and novelty hits with their trademark lightning-quick vocal syncopations, they also produced major hits in jazz, ballads, folk, country-western, seasonal, and religious titles, being the first Decca artists to record an album of gospel standards in 1950. Their versatility allowed them to pair with many different artists in the recording studios, producing Top 10 hits with the likes of Bing Crosby (the only recording Artist of the 1940s to sell more records than The Andrews Sisters), Danny Kaye, Dick Haymes, Carmen Miranda, Al Jolson, Ray McKinley, Burl Ives, Ernest Tubb, Red Foley, Dan Dailey, Alfred Apaka, and Les Paul. In personal appearances, on radio and on television, they sang with everyone from Rudy Vallee, Judy Garland and Nat "King" Cole to Jimmie Rodgers, Andy Williams, and The Supremes. Some of the trio's late-1930s recordings have noticeable Boswell Sisters vocal influences.

An ad in the 1951 Radio Annual showed photos of the Andrews as children, as contemporary Singers, and as old women in the then-future year of 1975; the act would not make it that long. In the 1950s, Patty Andrews decided to break away from the act to be a soloist. She had married the trio's Pianist, Walter Weschler, who became the group's manager and demanded more money for Patty. When Maxene and LaVerne learned of Patty's decision from newspaper gossip columns rather than from their own sister, it caused a bitter two-year separation, especially when Patty sued LaVerne for a larger share of their parents' estate. Patty attributed the breakup to the deaths of their parents: "We had been together nearly all our lives," Patty explained in 1971. "Then in one year our dream world ended. Our mother died (in 1948) and then our father (in 1949). All three of us were upset, and we were at each other's throats all the time." In 1951, they recorded The Windmill Song which is an adaptation of the French song Maître Pierre written in 1948 by Henri Betti (music) and Jacques Plante (lyrics). The English lyrics were written by Mitchell Parish. The Andrews Sisters formally broke up in 1953.

Maxene and LaVerne tried to continue the act as a duo and met with good press during a 10-day tour of Australia, but a reported suicide attempt by Maxene in December 1954 put a halt to any further tours (Maxene spent a short time in the hospital after swallowing 18 sleeping pills, an occurrence that LaVerne told reporters was an accident). Maxene and LaVerne did appear together on The Red Skelton Show on October 26, 1954 singing the humorous "Why Do They Give The Solos To Patty" as well as lip-synching "Beer Barrel Polka" with Skelton in drag filling in for Patty. This however did not sit well with Patty and a cease and desist order was sent to Skelton. The sisters' private relationship was often troubled and Patty blamed it on Maxene: "Ever since I was born, Maxene has been a Problem," she said.

The trio reunited in 1956 and signed a new recording deal with Capitol Records, for whom Patty was already a featured soloist. By this point however, rock-and-roll and doo-wop were dominating the charts and older artists were left by the wayside. The sisters recorded a dozen singles through 1959, some of which attempted to keep up with the times by incorporating rock sounds. None of these achieved any major success. In addition, they produced three hi-fi albums, including a vibrant LP of songs from the dancing 1920s with Billy May's orchestra. In 1962, they signed with Dot Records and recorded a series of stereo albums until 1964, both re-recordings of earlier hits which incorporated up-to-date production techniques, as well as new material, including "I Left My Heart In San Francisco", "Still", "The End of the World", "Puff the Magic Dragon", "Sailor", "Satin Doll", "Mr. Bass Man", the theme from Come September, and the theme from A Man and a Woman. They toured extensively during the 1960s, favoring top nightclubs in Las Vegas, Nevada, California, and London, England.

LaVerne Andrews married Lou Rogers, a trumpet player in Vic Schoen's band, in 1948. The two remained together until LaVerne's death from cancer on May 8, 1967 (Lou died in 1995). The ashes of LaVerne and Maxene Andrews are interred in the Columbarium of Memory of the Forest Lawn Memorial Park Cemetery in Glendale, California, close to the ashes of their parents.

After LaVerne died, Maxene and Patty continued to perform periodically until 1968, when Maxene decided she would become the Dean of Women at Tahoe Paradise College, teaching acting, drama and speech at a Lake Tahoe college and working with troubled teens, and Patty was once again eager to be a soloist.

In 1969, Patty appeared in Lucille Ball's third series Here's Lucy, in the sixth episode of the second season, titled "Lucy and the Andrews Sisters". The episode has Patty enlisting the help of Lucy, her daughter Kim (played by Lucie Arnaz), and her son Craig (Desi Arnaz Jr.) to perform a medley of Andrews Sisters hits for the Andrews Sisters Fan Club reunion. Lucy played LaVerne, Kim (Lucie Arnaz) played Maxene, and Craig (Desi Arnaz, Jr.) played Bing Crosby. She also had a cameo as herself along with many other stars in the 1970 film The Phynx.

Patty and Maxene's careers experienced a resurgence when Bette Midler covered "Boogie Woogie Bugle Boy" in 1973. The next year, the pair debuted on Broadway in the Sherman Brothers' nostalgic World War II musical: Over Here! which premiered at the Shubert Theatre to rave reviews. This was a follow-up to Patty's success in Victory Canteen, a 1971 California revue. Over Here! starred Maxene and Patty (with Janie Sell filling in for LaVerne and winning a Tony Award for her performance) and was written with both sisters in mind for the leads. It launched the careers of many now notable theater, film, and television stars, including John Travolta, Marilu Henner, Treat Williams and Ann Reinking. It was the last major hurrah for the sisters and was cut short owing to a conflict with the show's producers initiated by Patty's husband including a lawsuit he filed against the show's composers, the Sherman Brothers, quashing an extensively scheduled road tour. Over Here! lasted only a year, and its end marked the last time the sisters would ever sing together.

Patty continually distanced herself from Maxene, until her death, and would not explain her motives regarding the separation. People close to both sisters, including family members, believed that Patty's husband, Wally Weschler, was to blame. Maxene appealed to Patty for a reunion, personally if not professionally, both in public and in private, but to no avail. Maxene suffered a serious heart attack while performing in Illinois in 1982 and underwent quadruple bypass surgery, from which she successfully recovered. Patty visited her sister while she was hospitalized. Now sometimes appearing as "Patti" (but still signing autographs as "Patty") she re-emerged in the late 1970s as a regular panelist on The Gong Show. Maxene had a very successful comeback as a cabaret soloist in 1979 and toured worldwide for the next 15 years, recording a solo album in 1985 entitled "Maxene: An Andrews Sister" for Bainbridge Records. Patty started her own solo act in 1980, but did not receive the critical acclaim her sister had for her performances, even though Patty was considered to be the "star" of the group for years. The critics' major complaint was that Patty's show concentrated too much on Andrews Sisters material, which did not allow Patty's own talents as an expressive and bluesy vocalist to shine through.

The two sisters did reunite, albeit briefly, on October 1, 1987, when they received a star on Hollywood's Walk of Fame, even singing a few bars of "Beer Barrel Polka" for the Entertainment Tonight cameras. An earthquake shook the area that very morning and the ceremony was nearly cancelled, which caused Patty to joke, "Some people said that earthquake this morning was LaVerne because she couldn't be here, but really it was just Maxene and me on the telephone." Besides this, and a few brief private encounters, they remained somewhat estranged for the last few years.

Maxene Andrews married music publisher Lou Levy in 1941. They separated in 1949. Levy was the sisters' manager from 1937 to 1951. She died on October 21, 1995, after suffering a heart attack while vacationing on Cape Cod with her daughter/manager Lynda Wells.

The Andrews Sisters' harmonies and songs are still influential today, and have been copied and recorded by entertainers such as Bette Midler, Christina Aguilera, Pentatonix, and others. The group was inducted into the Vocal Group Hall of Fame in 1998. Writing for Bloomberg, Mark Schoifet said the sisters became the most popular female vocal group of the first half of the 20th century. They are still widely acclaimed today for their famous close harmonies. They were inducted into the Minnesota Rock/Country Hall of Fame in May of 2006.

Christina Aguilera used the Andrews Sisters' "Boogie Woogie Bugle Boy" to inspire her song "Candyman" (released as a single in 2007) from her hit album Back to Basics. The song was co-written by Linda Perry. The London-based trio the Puppini Sisters uses their style harmonies on several Andrews Sisters and other hits of the 1940s and 1950s as well as later rock and disco hits. The trio has said their name is a tribute to The Andrews Sisters. The National WW2 Museum's Victory Belles are proud to pay tribute to the Andrews Sisters performing their music daily in the Stage Door Canteen in New Orleans. The Manhattan Dolls, a New York City-based touring group, performs both the popular tunes sung by the Andrews Sisters and some of the more obscure tunes such as "Well Alright" and "South American Way" as well.

In 2008 and 2009, the BBC produced The Andrews Sisters: Queens of the Music Machines, a one-hour documentary on the history of the Andrews Sisters from their upbringing to the present. The American premier of the show was June 21, 2009, in their birthplace of Mound, Minnesota. In 2008, Mound dedicated "The Andrews Sisters Trail". The sisters spent summers in Mound with their uncles Pete and Ed Solie, who had a grocery store there. Maxene Andrews always said that the summers in Mound created a major sense of "normalcy" and "a wonderful childhood" in a life that otherwise centered on the sisters' careers. The Westonka Historical Society has a large collection of Andrews Sisters memorabilia.

Patty Andrews married agent Marty Melcher in 1947 and left him in 1949, when he pursued a romantic relationship with Doris Day. She then married Walter Weschler, the trio's Pianist, in 1951. Patty died of natural causes at her home in Northridge, California, on January 30, 2013 at the age of 94. Weschler, her husband of nearly 60 years, had died on August 28, 2010, at the age of 88.