Amidu's pivotal moment came when he exposed the infamous Woyome scandal, a financial misappropriation case that threatened to be Ghana's worst fiscal scandal at the time. The scandal involved illegal payments made to businessman Alfred Woyome. Amidu's audacity in confronting this issue earned him praise and criticism alike, as he fearlessly called out the wrongdoings, coining the term 'gargantuan' to describe the magnitude of the scandal.

Over the years, Amidu continued to climb the political ladder. He was appointed as Minister of Interior in January 2010 after a cabinet reshuffle. Some questioned his neutrality in handling the Bawku conflict due to his Builsa background, but he successfully navigated parliamentary vetting and assumed the role. Subsequently, he took on the roles of Attorney-General and Minister for Justice, further solidifying his position as a key figure in Ghanaian politics.

Amidu's principled stance against corruption did not sit well with everyone. In January 2012, President John Evans Atta Mills relieved him of his Attorney-General post, citing alleged misconduct during a meeting at the Osu Castle. Amidu made allegations regarding financial impropriety by another cabinet minister, and when asked to substantiate them, he faced dismissal. However, Amidu didn't back down; he challenged the legality of payments related to the Woyome scandal at the Supreme Court. The court ruled in favor of Amidu, ordering Alfred Woyome to refund the money to the state.

In 2018, Amidu's unwavering commitment to fighting corruption led to a historic moment in Ghana's political history. President Nana Akufo-Addo nominated him as Ghana's first Special Prosecutor, tasked with combating corruption in the newly created Office of the Special Prosecutor. Amidu's nomination garnered significant attention, and he was officially sworn into office in February 2018, vowing to fight corruption without fear or favor.

Former Special Prosecutor Martin Amidu has criticized his successor, Kissi Adjabeng, for allegedly suppressing investigations into bribery cases against Anas Aremeyaw Anas. Amidu revealed this in his latest epistle titled, “The Special Prosecutor Blackmails the Government by Prosecutions of Former Government Appointees.” He claimed that upon assuming office, Adjabeng also suppressed nearly completed investigations into three distinct corruption and public procurement malpractice cases involving Tekstart Africa Limited (Tekstart) and the National Lotteries Authority (NLA).