He was educated at Fort Hare University in South Africa.
In 1951 he wrote a long memorandum arguing against federation with Southern Rhodesia which was presented to Colonial Secretary James Griffiths and Commonwealth Relations Secretary Patrick Gordon-Walker during their visit to Nyasaland, in August and September 1951, to gauge Africans' sentiments on this subject. During the Lancaster House Conference convened in 1952 to discuss federation, wearing academic robes he "captivated crowds with his carefully argued attacks on the federal plan at village markets and meeting halls." He had by this time already been in correspondence for four years with Hastings Banda, who was to become the president of the country after independence. Despite widespread opposition, Nyasaland was integrated into the Federation of Rhodesia and Nyasaland in 1953. In 1954, Chirwa joined with Charles Matinga and Andrew Mponda in forming the short-lived Nyasaland Progressive Association, dedicated to working within the new reality of the federation. During 1954 - 1956, approximately, Chirwa was an instructor at Domasi Teacher Training College, where, along with David Rubadiri and Alec Nyasulu, he reportedly was active in infusing his students with nationalist political consciousness.
In Zomba Prison Orton Chirwa was held in solitary confinement and not allowed any outside contact. For eight years he was not even permitted to see his wife Vera who was being held in the same prison. In 1990 Amnesty International launched an investigation into their fate and named the couple prisoners of conscience. In autumn 1992, when a delegation of British legal experts was allowed to visit Orton and Vera at the prison, the Chirwas were able to meet again for the first time in 8 years. According to the British lawyers, at the time of the meeting he was partially deaf and blind due to untreated cataracts. Orton died in his cell 3 weeks later at the age of 73.
In 1959 the British Colonial Government banned the Nyasaland African Congress (NAC) and arrested most of the political party's leaders, including Orton Chirwa and Banda in a mass swoop known as Operation Sunrise. Orton Chirwa was detained in Khami Jail near Bulawayo in Southern Rhodesia for a short time before, on August 1, 1959, being released. He became the first president of the Malawi Congress Party(MCP), a successor-party to the NAC formed on September 30, 1959. There was some opposition to this appointment, notably from Kanyama Chiume, who considered him tainted by his previous association with the Federation-tolerant Nyasaland Progressive Association. It has been suggested that the British government might have harbored hopes of Chirwa taking the leadership reins as a moderate nationalist, but it soon became clear that he was merely "keeping the seat warm" for Banda. In November 1959 when he visited Iain Macleod, the Colonial Secretary in the Conservative government under Harold Macmillan, he made clear that MCP would only negotiate independence with Banda as its head. Three days after Banda was released from Gwelo Prison on April 2, 1960, Orton Chirwa together with other NAC leaders invited him to stand for President of the MCP. Chirwa stood down and Dr. Banda took over the leadership of the Malawi Congress Party which subsequently led Malawi to independence in 1964.
Harold MacMillan visited Nyasaland in 1960, and Chirwa organized a protest on January 25 in Blantyre which was noted in the British newspapers for its rowdiness. During the run-up to elections in 1962 and again in 1963, he was vocal in his condemnation of attempts by other Africans to form political parties in opposition to the MCP, with himself and David Rubadira by this time openly advocating totalitarian rule by the MCP.
Orton Chirwa was named Parliamentary Secretary in the Ministry of Justice, (a position slightly short of Minister) in Dr. Banda's interim administration which took office in 1962. In the run-up to the 1964 National Assembly elections, he was active in promoting the use of "traditional courts" as an alternative to the existing judiciary, a controversial move in that these courts were subject to significant political influence, and was heavily criticised by the Chief Justice for this and by the Governor, Glyn Jones, for failing to investigate and prosecute hundreds of cases of politically motivated intimidation, in the form of assaults, murders, arson and crop destruction, as well as cases of intimation against Jehovah's Witnesses. In 1963, he threatened to bring charges against the Nyasaland Times under the Sedition Act because of that newspaper's reporting on opposition political parties.
Nkhonda Chirwa, second son of Orton and Vera, died unexpectedly on 18 October 2016 in Kendal, Cumbria, England, hometown for him and his children for many years. He is buried in Parkside cemetery Kendal. A very popular man in the town, he will be sorely missed. At his funeral tributes were paid to Amnesty International for their efforts on behalf of the Chirwa family. Orton Chirwa's grandson, Orton Ndau is also a lawyer. Orton Ndau graduated from the Howard University School of Law in 2011. Thereafter, Orton Ndau clerked for Kevin N. Fox, Chief Magistrate for the United States District Court for the Southern District of New York. Orton Ndau is now a lawyer at Paul, Weiss, Rifkind, Wharton & Garrison LLP in New York.