A military brat, Khalifa, whose real name is Cameron Thomaz, was born in 1987 in Minot, North Dakota. After his parents divorced when he was three, he lived in various places and military bases around the world. His first attempt at committing lyrics to paper was around age nine, and at 12 he was already recording and producing his own records in his father's Oklahoma studio. Settling in Pittsburgh during his high school years, Khalifa laid down the groundwork for a solo career and kept busy recording music in a local studio, I.D. Labs. He stood out among the studio's regulars, prompting the I.D. Labs' staff to offer him free beats and recording time, plus bringing him to the attention of Benjy Grinberg, a former executive assistant to L.A. Reid at Arista Records who had started up a new independent label, Rostrum Records. Signed to Rostrum, Khalifa built a buzz in Pittsburgh with a few singles, but he began to draw ears nationally during his senior year in high school when his first mixtape, Prince of the City: Welcome to Pistolvania, dropped in early 2006. With the release of his independent full-length debut, Show and Prove, later that year, major publications, including Vibe, XXL, and Rolling Stone, featured profiles on the young rapper.

In summer 2007, Khalifa and Rostrum hopped on board with Warner and he cut his first major-label single, "Young'n on His Grind." The follow-up, “Say Yeah,” climbed into the Top 20 of Billboard's Hot Rap Tracks that same year, but the relationship between Warner Bros. and Khalifa was taking a turn for the worse. Unable to come to an agreement on his debut album for the label, the rapper announced he was leaving Warner in 2009 and returning to Rostrum for the album Deal or No Deal.

The next year began with Khalifa appearing on the cover of XXL as one of the magazine’s Top Ten Freshmen while The Source named him Rookie of the Year. In April his Kush & Orange Juice mixtape topped Google’s Hot Search Trends list. Atlantic took notice, signing the artist that same month, and in September, his first single for the label, the Pittsburgh Steelers tribute and Stargate production “Black and Yellow,” appeared. As the NFL team progressed toward the playoffs, Khalifa’s track became their unofficial anthem, and when the Green Bay Packers emerged as the team’s opponent for the Super Bowl, Lil Wayne responded with the answer song “Green and Yellow.” Khalifa’s song topped the charts in February of 2011, while his debut Atlantic set, Rolling Papers, debuted at number two on the U.S. Billboard 200 chart a month later. Also arriving that same year was a feature film with Snoop Dogg, Mac and Devin Go to High School, along with its accompanying soundtrack. Two mixtapes, Taylor Allderdice and Still Blazin', landed in 2012 and in early December, his fourth album, O.N.I.F.C., was released, featuring a return appearance by production team Stargate, this time working with Benny Blanco on the album's first single "Work Hard, Play Hard." Khalifa explained in interviews that the acronym title O.N.I.F.C. stood for "Only Nigga in First Class," inspired by by the album H.N.I.C. by Prodigy of Mobb Deep. Clean copies saw the abbreviation standing for "One Night in First Class."