While in his teens, he acquired a taste for percussion-based avant-garde composers such as Edgard Varèse and 1950s rhythm and blues music. He began writing classical music in high school, while at the same time playing drums in rhythm and blues bands—he later switched to electric guitar. He was a self-taught composer and performer, and his diverse musical influences led him to create music that was often impossible to categorize. His 1966 debut album with the Mothers of Invention, Freak Out!, combined songs in conventional rock and roll format with collective improvisations and studio-generated sound collages. His later albums shared this eclectic and experimental approach, irrespective of whether the fundamental format was one of rock, jazz or classical. He wrote the lyrics to all his songs, which—often humorously—reflected his iconoclastic view of established social and political processes, structures and movements. He was a strident critic of mainstream education and organized religion, and a forthright and passionate advocate for freedom of speech, autodidacticism and the abolition of censorship.

Zappa was a highly productive and prolific artist and he gained widespread critical acclaim. Many of his albums are considered essential in rock and jazz history. He is regarded as one of the most original guitarists and composers of his time. He also remains a major influence on musicians and composers. He had some commercial success, particularly in Europe, and for most of his career was able to work as an independent artist. Zappa was posthumously inducted into the Rock and Roll Hall of Fame in 1995 and received the Grammy Lifetime Achievement Award in 1997.

Zappa was married to Kathryn J. "Kay" Sherman from 1960 to 1964. In 1967 he married Adelaide Gail Sloatman, with whom he remained until his death from prostate cancer in 1993. They had four children: Moon Unit, Dweezil, Ahmet Emuukha Rodan and Diva Thin Muffin Pigeen. Gail Zappa manages the businesses of her late husband under the name the Zappa Family Trust.

Frank Zappa was born in Baltimore, Maryland, on December 21, 1940. His mother, Rose Marie (née Colimore), was of Italian and French descent, and his father, Francis Vincent Zappa, was a native of Partinico, Sicily and had Greek and Arab ancestry. Zappa was the eldest of four children, and had two brothers and a sister. The family moved often during Zappa's childhood because his father, a chemist and mathematician, had various jobs in the US defense industry. After a brief time in Florida in the mid-1940s, the family returned to Maryland, where Zappa's father worked at the Edgewood Arsenal chemical warfare facility at the Aberdeen Proving Ground. Due to their home's proximity to the arsenal, which stored mustard gas, gas masks were kept in the house in case of an accident. This had a profound effect on the young Zappa: references to germs, germ warfare and other aspects of the defense industry occur throughout his work.

During his childhood Zappa was often sick, suffering from asthma, earaches and sinus problems. A doctor treated the latter by inserting a pellet of radium into each of Zappa's nostrils; little was known at the time about the potential dangers of being subjected to even small amounts of therapeutic radiation. Nasal imagery and references appear both in his music and lyrics, as well as in the collage album covers created by his long-time visual collaborator, Cal Schenkel.

Many of Zappa's childhood diseases may have arisen from exposure to mustard gas; furthermore, his health worsened when he lived in the Baltimore area. In 1952, his family relocated mainly because of Zappa's health. They next moved to Monterey, California, where Zappa's father taught metallurgy at the Naval Postgraduate School. Shortly afterward, they moved to Claremont, then to El Cajon before finally moving to San Diego.

Since I didn't have any kind of formal training, it didn't make any difference to me if I was listening to Lightnin' Slim, or a vocal group called the Jewels ... , or Webern, or Varèse, or Stravinsky. To me it was all good music.

Zappa joined his first band, The Ramblers, at Mission Bay High School in San Diego. He was the band's drummer. About the same time his parents bought a phonograph, which allowed him to develop his interest in music, and to begin building his record collection. R&B singles were early purchases, starting a large collection he kept for the rest of his life. He was interested in sounds for their own sake, particularly the sounds of drums and other percussion instruments. By age 12, he had obtained a snare drum and began learning the basics of orchestral percussion. Zappa's deep interest in modern classical music began when he read a LOOK magazine article about the Sam Goody record store chain that lauded its ability to sell an LP as obscure as The Complete Works of Edgard Varèse, Volume One. The article described Varèse's percussion composition Ionisation, produced by EMS Recordings, as "a weird jumble of drums and other unpleasant sounds". Zappa decided to seek out Varèse's music. After searching for over a year, Zappa found a copy (he noticed the LP because of the "mad scientist" looking photo of Varèse on the cover). Not having enough money with him, he persuaded the salesman to sell him the record at a discount. Thus began his lifelong passion for Varèse's music and that of other modern classical composers.

Zappa grew up influenced by avant-garde composers such as Varèse, Igor Stravinsky and Anton Webern, R&B and doo-wop groups (particularly local pachuco groups), and modern jazz. His own heterogeneous ethnic background, and the diverse social and cultural mix in and around greater Los Angeles, were crucial in the formation of Zappa as a practitioner of underground music and of his later distrustful and openly critical attitude towards "mainstream" social, political and musical movements. He frequently lampooned musical fads like psychedelia, rock opera and disco. Television also exerted a strong influence, as demonstrated by quotations from show themes and advertising jingles found in his later works.

By 1956, the Zappa family had moved to Lancaster, a small aerospace and farming town in the Antelope Valley of the Mojave Desert close to Edwards Air Force Base, in northern Los Angeles County. Zappa's mother encouraged him in his musical interests. Although she disliked Varèse's music, she was indulgent enough to give her son a long distance call to the composer as a 15th birthday present. Unfortunately, Varèse was in Europe at the time, so Zappa spoke to the composer's wife. He later received a letter from Varèse thanking him for his interest, and telling him about a composition he was working on called "Déserts". Living in the desert town of Lancaster, Zappa found this very exciting. Varèse invited him to visit if he ever came to New York. The meeting never took place (Varèse died in 1965), but Zappa framed the letter and kept it on display for the rest of his life.