Antasari started his career at the Justice Ministry. His plan to become a diplomat changed after he was accepted to become a prosecutor at the Central Jakarta State Prosecutor's Office, where he served from 1985 to 1989. Next he was appointed as a prosecutor at Tanjung Pinang State Prosecutor's Office. He then served as Head of the Corruption Investigation Section at the Lampung High State Prosecutor's Office and later as Head of Special Crimes at the West Jakarta State Prosecutor's Office. Next, he became Baturaja State Prosecutor. In 1999, Antasari joined the High State Prosecutor's Office, serving as chief investigator of the Special Crimes Sub-directorate. He was subsequently Head of Mass Media Communication at the High State Prosecutor's Office. It was as Chief of the South Jakarta State Prosecutor's Office that he first gained widespread attention in the mass media. In 2000, the Supreme Court sentenced former president Suharto's youngest sonTommy to 18 months in jail for corruption. It was Antasari's job to take Tommy to jail, but instead the former playboy was allowed to go on the run, resulting in speculation that Antasari had been paid off, although this was never proved.
Chairman of Corruption Eradication Commission
The controversy over Tommy Suharto's case did not stop Antasari from being elected Chairman of the Indonesian Corruption Eradication Commission in December 2007, defeating Chandra M. Hamzah by 41 votes in the election held by the 49 members of the Indonesian House of Representatives' Commission III on legal affairs. His election victory was attributed to strong lobbying by Golkar Party and the Indonesian Democratic Party of Struggle.
Murder case
On 4 May 2009, Antasari was arrested on suspicion of ordering the murder of Nasrudin Zulkarnaen, a prominent businessman who headed a state-owned pharmaceuticals firm, PT Rajawali Putra Banjaran. It was alleged that Nasrudin had been blackmailing Antasari over the latter's extramarital affair with a female golf caddy. Also arrested in connection with the murder were tycoon Sigid Haryo Wibisono, the former head of Golkar's Central Java chapter and chief commissioner of the Harian Merdeka newspaper; and Senior Commissioner Wiliardi Wizar, the former South Jakarta Police chief. Six men involved in planning and conducting the assassination was also detained. Williardi was accused of hiring the hit squad and Sigid was accused of paying for the hit. Antasari denied any wrongdoing, claiming he was faithful to his wife, Ida Laksmiwati, of 26 years. He was suspended as KPK chairman by President Susilo Bambang Yudhoyono. On 11 February 2010, Antasari was convicted of ordering the murder and sentenced to 18 years' imprisonment. He appealed the verdict unsuccessfully.
Clemency
Antasari was granted clemency on 26 January 2017 by President Joko Widodo. He claims that the murder case was manipulated by President Yudhoyono for political reasons.
Advice
Antasari's advice to his daughter at the time of her marriage was: "Treasure is not valuable in the world, but the prayers and alms are the best in the world."