Killer Mike released his debut album, Monster, in 2003. The album's lead single was "Akshon (Yeah!)", which featured OutKast on guest vocals, and was included on the soundtrack to the 2004 version of EA Sports popular video game Madden NFL. He even made a Madden '04 remix of "Akshon (Yeah!)" for the game. The album's second single was "A.D.I.D.A.S.", featuring Big Boi and Sleepy Brown, which peaked at #60 on the Billboard Hot 100. It is Killer Mike's highest charting single to date as a lead artist. The song's title was an acronym for "All day I dream about sex". Following the release of his own material, he appeared on "Flip Flop Rock" and "Bust" on the Speakerboxx half of Speakerboxxx/The Love Below. He also appeared on "Southern Takeover" with Pastor Troy on Chamillionaire's CD The Sound of Revenge. Killer Mike appeared on the song "Never Scared" by fellow rapper Bone Crusher, also with T.I., from AttenCHUN! It peaked at #26 on the Hot 100, becoming Mike's second top 40 hit("The Whole World" being the first). The song was also used on the Madden NFL 04 game and even by the Atlanta Braves for their 2003 season. His second album Ghetto Extraordinary has had its release date pushed back several times due to disputes between Big Boi and Sony Records.
Killer Mike has also performed as a voice actor. He played a rapper/actor, turned President of the United States, named Taqu'il in the Adult Swim cartoon Frisky Dingo. According to an article published in the June 2007 issue of XXL, Killer Mike addressed why he left the Purple Ribbon roster. He stated that he felt as if Purple Ribbon was the equivalent to the "Clippers," while he wanted to join the "Lakers."
Days after T.I. addressed the rumor and confirmed that he and Killer Mike had been in talks about bringing Mike to his Grand Hustle imprint on Atlantic, Killer Mike confirmed to HipHopDX.com that he signed.
In 2012, Killer Mike formed an association with rapper/producer El-P, who produced Mike's album R.A.P. Music. That same year, he guested on El-P's album Cancer 4 Cure. In 2013, they formed the duo Run the Jewels and released a free album of the same name on June 26.
Killer Mike opened a barbershop with his wife, Shana Render, on November 1, 2011. The two acquired and reworked a barbershop in Atlanta, Georgia, and named it Graffiti's SWAG. He told Barber-Schools.org that he waited 9 years before choosing to open the barbershop, and it took his wife advising him to do it now while he had the time and money to pursue his lifelong dream. He also said he aims to open 150 shops across the U.S. over time, predominantly in cities with large Black communities. The barbershop is decorated with artwork on the walls honoring historic black leaders like Dr. Martin Luther King. Killer Mike said that he hopes to "lift up men in the community who are out of work and help move them toward sustainable, lifelong careers" and give his employees "opportunity for real economic elevation." The shop currently employs six barbers, and they plan to add four to six more licensed barbers to the team. Killer Mike also says that he hopes to pursue his own barber license in the winter of 2012. Graffiti's SWAG Barbershop is located at 3461 Roosevelt Highway, Suite 316, Atlanta, Georgia 30349.