John Rzeznik, also known as Johnny Rzeznik, was born on December 5, 1965 in Buffalo, New York, the youngest of five children, to Joseph and Edith Rzeznik. John Rzeznik had a strict Catholic upbringing on Buffalo's working-class East Side. Rzeznik's father died from complications of alcoholism at the age of fifty five when John was fourteen years old. Just over a year later his mother died from a sudden heart attack - by the age of only sixteen John had lost both of his parents and was to be brought up by his four older sisters. It was during this period and while attending high school that John picked up what would become a life-long hobby and vocation, playing the guitar. Soon after he would get an apartment on his own and become a punk. In 1986, while studying to become a plumber at Buffalo's McKinley Vocational High School, he formed the band that became the Goo Goo Dolls with Robby Takac. Previously John had been in a band with Robby's cousin, called The Beaumonts. The band were originally called the Sex Maggots, but this was changed on a whim to The Goo Goo Dolls (from an ad in a True Detective magazine) when a concert promoter asked them to, fearing the local newspapers would not print an advert for a show featuring a band with such a name.

In the early days the band gigged relentlessly, with Robby as the frontman. They were soon picked up by a small record label, Celluloid. Under Celluloid they released their first eponymous album on a $750 budget. This would attract the attention of a larger record label, Metal Blade, who would release their next few albums. For the next few years the band would tour, produce albums and hold down regular jobs. In 1990 he met his future wife, fashion model Laurie Farinacci, also from Buffalo, who he would marry in 1993. Despite the band receiving regular airplay on college radio, it wouldn't be until 1995's A Boy Named Goo that they would have a major hit. That hit came with the release of the single "Name", an acoustic ballad sung by Rzeznik which received massive airplay and led to platinum sales for the album.

Following the success of A Boy Named Goo, Rzeznik suffered a severe case of writer's block. His writer's block was finally overcome, when in 1997 the band were released from their contract with Metal Blade to sign with Warner Bros. Records, and approached to write a song for the soundtrack to the film City of Angels. Rzeznik watched the film and was inspired to write "Iris", which would become the band's biggest hit and signature song. The film and song were both a huge success, with Iris spending a record eighteen weeks at the top of the Hot 100 Airplay Chart. The band followed up with the hit album Dizzy Up The Girl, which in addition to "Iris" contained another 4 Top 10 singles and sold over 3 million copies.

In 2002 Rzeznik was divorced from his wife. This event influenced his songwriting for the band's next album Gutterflower, which was considered to be somewhat darker lyrically than the previous album. This album was also a success, though not on the scale of Dizzy Up the Girl or A Boy Named Goo, going Gold and producing the hit singles "Here Is Gone," "Big Machine," and "Sympathy."

Following the album Gutterflower, Rzeznik wrote "Always Know Where You Are" and "I'm Still Here" for the Disney film Treasure Planet, which were also released as a single independently from the band.

On May 19, 2008, John Rzeznik was inducted into the Songwriters Hall of Fame.