At age 17, he was the youngest war correspondent to cover the Korean War for The Manila Times of Don Joaquín "Chino" Roces.

Because of his journalistic feats, he received the Philippine Legion of Honor award from President Elpidio Quirino at age 18.

At 21, he became a close adviser to then Defense Secretary Ramon Magsaysay. Aquino took up law at the University of the Philippines, where he became a member of Upsilon Sigma Phi, the same fraternity as Ferdinand Marcos. He interrupted his studies again however to pursue a career in journalism. According to Máximo Soliven, Aquino "later 'explained' that he had decided to go to as many schools as possible, so that he could make as many new friends as possible."

In early 1954, he was appointed by President Ramon Magsaysay, his wedding sponsor to his 1953 wedding at the Our Lady of Sorrows Church in Pasay with Corazon Cojuangco, to act as personal emissary to Luis Taruc, leader of the Hukbalahap rebel group. After four months of negotiations, he was credited for Taruc's unconditional surrender and was given a second Philippine Legion of Honor award with the degree of Commander on October 14, 1954. On October 11, 1954, he married Corazon "Cory" Sumulong Cojuangco in Pasay City, with whom he had five children (four daughters and a son).

He became mayor of Concepcion in 1955 at the age of 22.

Five years later, he was elected the nation's youngest vice-governor at 27.

Two years later he became governor of Tarlac province in 1961 at age 29.

He became the secretary-general of the Liberal Party in 1966.

In 1967 he became the youngest elected senator in the country's history at age 34.

In 1968, during his first year as senator, Aquino alleged that Marcos was on the road to establishing "a garrison state" by "ballooning the armed forces budget", saddling the defense establishment with "overstaying generals" and "militarizing our civilian government offices".

Aquino became known as a constant critic of the Marcos regime, as his flamboyant rhetoric had made him a darling of the media. His most polemical speech, "A Pantheon for Imelda", was delivered on February 10, 1969. He assailed the Cultural Center, the first project of First Lady Imelda Marcos as extravagant, and dubbed it "a monument to shame" and labelled its designer "a megalomaniac, with a penchant to captivate". By the end of the day, the country's broadsheets had blared that he labelled the President's wife, his cousin Paz's former ward, and a woman he had once courted, "the Philippines' Eva Peron". President Marcos is said to have been outraged and labelled Aquino "a congenital liar". The First Lady's friends angrily accused Aquino of being "ungallant". These so-called "fiscalization" tactics of Aquino quickly became his trademark in the Senate.

It was not until the Plaza Miranda bombing however—on August 21, 1971, 12 years to the day before Aquino's own assassination—that the pattern of direct confrontation between Marcos and Aquino emerged. At 9:15 pm, at the kick-off rally of the Liberal Party, the candidates had formed a line on a makeshift platform and were raising their hands as the crowd applauded. The band played, a fireworks display drew all eyes, when suddenly there were two loud explosions that obviously were not part of the show. In an instant the stage became a scene of wild carnage. The police later discovered two fragmentation grenades that had been thrown at the stage by "unknown persons". Eight people died, and 120 others were wounded, many critically. While Aquino was not present at the incident, the event rose to further political confrontation.

President Marcos declared martial law on September 21, 1972 through proclamation 1081 and he went on air to broadcast his declaration on midnight of September 23. Aquino was one of the first to be arrested and imprisoned on trumped-up charges of murder, illegal possession of firearms and subversion. He was tried before Military Commission No. 2 headed by Major-General Jose Syjuco.

On April 4, 1975, Aquino announced that he was going on a hunger strike, a fast to the death to protest the injustices of his military trial. Ten days through his hunger strike, he instructed his lawyers to withdraw all motions he had submitted to the Supreme Court. As weeks went by, he subsisted solely on salt tablets, sodium bicarbonate, amino acids, and two glasses of water a day. Even as he grew weaker, suffering from chills and cramps, soldiers forcibly dragged him to the military tribunal's session. His family and hundreds of friends and supporters heard Mass nightly at the Santuario de San Jose in Greenhills, San Juan, praying for his survival. Near the end, Aquino's weight had dropped from 54 to 36 kilos. Aquino nonetheless was able to walk throughout his ordeal. On May 13, 1975, on the 40th day, his family and several priests and friends, begged him to end his fast, pointing out that even Christ fasted only for 40 days. He acquiesced, confident that he had made a symbolic gesture. But he remained in prison, and the trial continued, drawn out for several years.

On November 25, 1977, the Military Commission found Aquino guilty of all charges and sentenced him to death by firing squad.

In mid-March 1980, Aquino suffered a heart attack, possibly the result of seven years in prison, mostly in a solitary cell. He was transported to the Philippine Heart Center, where he suffered a second heart attack. ECG and other tests showed that he had a blocked artery. Philippine surgeons were reluctant to do a coronary bypass, because it could involve them in a controversy. In addition, Aquino refused to submit himself to Philippine doctors, fearing possible Marcos "duplicity"; he preferred to go to the United States for the procedure or return to his cell at Fort Bonifacio and die.

Making up for the lost time as the family's breadwinner, he toured America; attending symposiums, lectures, and giving speeches in freedom rallies opposing the Marcos dictatorship. The most memorable was held at the Wilshire Ebell Theater in Los Angeles, California on February 15, 1981.

In the first quarter of 1983, Aquino received news about the deteriorating political situation in his country and the rumored declining health of President Marcos (due to lupus). He believed that it was expedient for him to speak to Marcos and present to him his rationale for the country's return to democracy, before extremists took over and made such a change impossible. Moreover, his years of absence made his allies worry that the Filipinos might have resigned themselves to Marcos' strongman rule and that without his leadership the centrist opposition would die a natural death.
He left Logan International Airport on August 13, 1983, took a circuitous route home from Boston, via Los Angeles to Singapore. He then left for Hong Kong and on to Taipei. From Taipei he flew to Manila on then Taiwan's flag carrier China Airlines Flight 811.
Aquino was assassinated on August 21, 1983, when he was shot in the head after returning to the country. At the time, bodyguards were assigned to him by the Marcos government.

The remainder of his personal and political life had a distinct spiritual sheen. He emerged as a contemporary counterpart of Jose Rizal, who was among the most vocal proponents of the use of non-violence to combat a repressive regime at the time, following the model of Gandhi and Martin Luther King. Some remained skeptical of Aquino's redirected spiritual focus, but it ultimately had an effect on his wife's political career. While some may question the prominence given Aquino in Philippine history, it was his assassination that was pivotal to the downfall of a despotic ruler and the eventual restoration of democracy in the Philippines.