Dwayne Michael Carter Jr. grew up as an only child (he now has a younger brother) in the poverty-stricken and crime-ridden Hollygrove neighbourhood of New Orleans' 17th Ward. At the age of sixteen, his stepfather Reginald "Rabbit" Carter died.

Wayne's first contact with hip-hop was listening to local Cash Money Records artists like Pimp Daddy and U.N.L.V., whom he would credit as his earliest influences. Wayne began rapping at block parties as a child, and his performance at one of them caught the ear of Lil Slim, a Cash Money rapper also from the neighborhood, who soon after the show gave him his phone number. He went on an autograph signing session with Lil Slim, he met Cash Money Records owners, Brian "Baby" Williams and Ronald "Slim" Williams. His freestyling abilities impressed the Williams brothers, but they didn't sign him at first. 11-year old Wayne started to record freestyles on Baby's answering machine and haunted Cash Money offices nearly every day. When Baby saw so much engagement in the young rapper, he soon signed him and hooked up with another newcomer Lil' Doogie (who would later become famous as B.G.) to form The B.G.'z. The group released their first and only album, True Story, in 1995.

In 1997, Wayne formed the Hot Boys along with Juvenile, Turk, and B.G., and they released their seminal debut CD Get It How You Live. The record's success earned the young teenagers fans throughout the south and midwest. He further distinguished himself on the Hot Boys' platinum selling Universal debut Guerilla Warfare released in 1998, followed by their 2003 release Let Em Burn.

In 1999, Wayne launched his solo career with the release of Tha Block Is Hot. This was followed by Lights Out in 2000 and 500 Degreez in 2002, an allusion to Juvenile's 400 Degreez.

In 2004, Wayne Carter released Tha Carter. This album is marked as a personal milestone as he claimed to have finally perfected his trade. It was also Tha Carter that finally earned him mass notability outside the south as a talented lyricist, because at that time southern rappers were stereotyped as having little to no lyrical ability.

On December 6, 2005 Wayne released Tha Carter II noticeably producing the album without the prominent beats of Mannie Fresh. Tha Carter II sold more than 238,000 copies debuting at no. 2 on the Billboard Top 200 albums chart and has been certified platinum. The lead single off the album, "Fireman", became a hit in the US, peaking at 32 on the Billboard Hot 100 chart. The second single, "Grown Man", was solicited to urban radios in January of 2006 in hopes of spreading to Top 40 Mainstream and then to the Hot 100, but failed to do so and failed to receive any attention due to lack of promotion and no video.[citation needed] The third single "Hustler Musik" received a video and gained minor attention also. "Hustler Musik" reached #87 on the Billboard Hot 100.

Recently Wayne was recruited by the Boyz N Da Hood as their fourth member after Young Jeezy left the group to engage in his solo career. Due to scheduling conflicts involving the promotion of Tha Carter II, he would never be formally named an active member of Boyz N Da Hood but maintains a very good relationship with the group recording new tracks with them often. Florida rapper Rick Ross was rumored to then replace Wayne and in essence, Young Jeezy but he also has denied that he will be an official member of the group. Lil Wayne will also be featured on Roman Verone's up coming mix CD and LP due out soon.

In 2006 Lil Wayne released his critically acclaimed sequel to his Dedication mixtape with DJ Drama called Dedication 2. On it, he included an outro track entitled "Georgia....Bush" on which he addresses the problems surrounding the government's response to Hurricane Katrina in his native New Orleans, Lousiana and also places a large amount of blame on President George W. Bush. The title comes from the chorus lyric: "Hurrican Katrina, we shoulda called it Hurricane Georgia Bush." The track was recorded on the beat to Ludacris' single "Georgia" which sampled the Ray Charles track "Georgia On My Mind". This song is followed by a freestyle called "Weezy's Ambitions" over Tupac Shakur's "Ambitionz Az a Ridah". The freestyle was originally done on BET'sRap City following the release of Tha Carter II.

Lil Wayne is set to release two collaboration LPs. Originally, the mixtape I Can't Feel My Face with Juelz Santana was released over the summer, but with its extreme demand and popularity, there are now rumors of it becoming a major-label commercially released LP. On October 31 2006, Wayne released an album with his mentor Baby: Like Father, Like Son. Many confuse Baby as Wayne's birth father, but this is not true, as evidenced by Wayne's singles "Everything" (from Lights Out), and a song on Like Father, Like Son, where Wayne says "My dad died when I was 16." Later in the month of April of 2007 Lil Wayne released a new mixtape album called "Da Drought 3".