Maithripala Sirisena was born on 3 September 1951 in Yagoda, a village in present-day Gampaha District. He is the son of World War II veteran Albert Sirisena, who was awarded five acres of paddy land in Polonnaruwa near Parakrama Samudra by D. S. Senanayake. His mother was a school Teacher.

He was educated at Thopawewa Maha Vidyalaya and Royal College, Polonnaruwa where he first developed an interest in politics. While still in school, as a teenager, Sirisena became interested in communism and joined the Communist Party becoming closely associated with party leader N. Shanmugathasan in party activities. In 1968 he took part in a communist party anti-government rally which was broken up by baton charging police.

At the age of 17 years he was chosen as the secretary of the SLFP Youth Organisation in Polonnaruwa by the SLFP Member of Parliament for Polonnaruwa, Leelaratna Wijesingha. In 1971, aged 19, he was jailed for 15 months for alleged involvement in the Janatha Vimukthi Peramuna Insurrection. Following his release from prison, Sirisena joined All Ceylon SLFP Youth Organization led by Anura Bandaranaike and joined politics at the national level. After serving at a number of state institutions, Sirisena obtained the SLFP membership in 1978. In 1974 Sirisena started working at the Palugasdamana Multi Purpose Cooperative Society as a purchasing office and in 1976 he became a grama niladhari (village officer) but resigned in 1978. He rose up the SLFP ranks, joining its politburo in 1981, where he was chosen as the President of the All Island SLFP Youth Organisation, and also later served as Treasurer. During the 1981 Presidential poll, when Basil Rajapaksa joined the United National Party, he took over the responsibility of the Secretary of the organisation. Subsequently, he was appointed the Polonnaruwa SLFP chief organiser by the SLFP hierarchy. He became President of the All Island SLFP Youth Organisation in 1983.

Sirisena studied for three years at the Sri Lanka School of Agriculture, Kundasale from where he earned a diploma in agriculture in 1973. In 1980 he earned a Diploma in political science at the Maxim Gorky Literature Institute in Russia.

Sirisena contested the 1989 parliamentary election as one of the SLFP's candidates in Polonnaruwa District and was elected to the Parliament. He was re-elected at the 1994 parliamentary election, this time as a People's Alliance (PA) candidate. In 1997 he was appointed as the General Secretary of the SLFP for the first time, from which he later resigned. In August 2000 Sirisena tried to become general-secretary of the SLFP but was beaten by S. B. Dissanayake. Sirisena was instead appointed one the Deputy Presidents of SLFP. He became general-secretary of the SLFP in October 2001 following Dissanayake's defection to the United National Party (UNP).

Sirisena was appointed Deputy Minister of Irrigation in the new PA government led by Chandrika Kumaratunga in 1994. In 1997 President Kumaratunga promoted him to the Cabinet, appointing him Minister of Mahaweli Development. While in this office he initiated many concessionary grants to improve the standard of the farming community. He was also responsible for influencing the government's decision to give farmers a bag of fertilizer for Rs. 350 in order to combat the food crisis at the time. He also saved the Paddy Marketing Board from privatization converting it into a government institution when he became the Agriculture Minister, in 2005. The Paddy Marketing Board continues to regulate the prices of paddy to this day. He also began important irrigation projects such as Moragahakanda, Kalu and Walawe rivers. He was re-elected to Parliament at the 2000 parliamentary election and retained his ministerial portfolio.

He was re-elected at the 2001 parliamentary election but the PA lost the election and so Sirisena lost his ministerial position.

In January 2004 the SLFP joined forced with the Janatha Vimukthi Peramuna to form a political alliance called the United People's Freedom Alliance (UPFA). Sirisena was re-elected at the 2004 parliamentary election as a UPFA candidate. President Kumaratunga appointed him Minister of River Basin Development and Rajarata Development in the new UPFA government in April 2004. He was also appointed Leader of the House. Sirisena's ministerial portfolio was renamed as Minister of Irrigation, Mahaweli and Rajarata Development in July 2005. He resigned as Leader of the House in August 2005.

After the 2005 presidential election newly elected President Mahinda Rajapaksa appointed Sirisena Minister of Agriculture, Environment, Irrigation and Mahaweli Development in November 2005. On 27 March 2006 Sirisena's personal secretary M. L. Dharmasiri was shot dead by unknown gunmen in Aranangawila. Following a cabinet reshuffle in January 2007 he was appointed Minister of Agricultural Development and Agrarian Services Development by President Rajapaksa.

In order to combat the 2007–08 world food price crisis, Sirisena initiated a plan under the scheme ‘Api Wavamu – Rata Nagamu’ to improve local food production on national scale. Festivals of tilling were conducted in each divisional secretariat every year leading to the re cultivation of more than 1 million abandoned paddy fields under the programme. The project was considered a great success being acknowledged as his green revolution.

Sirisena has claimed that LTTE may have tried to assassinate him on at least five occasions. Sirisena narrowly escaped death on 9 October 2008 when a convoy he was part of was attacked by a Liberation Tigers of Tamil Eelam's suicide bomber at Piriwena Junction in Boralesgamuwa, Colombo. One person was killed and seven injured.

Sirisena was re-elected at the 2010 parliamentary election and was appointed Minister of Health in April 2010. During his time Sirisena sought to combat cigarette and alcohol consumption within the country. He introduced a National Medicinal Drug Policy based on that of the Sri Lanka National Pharmaceuticals Policy of Seneka Bibile and brought the Cigarette and Alcohol act to parliament against cigarette packaging that include pictorial warnings. The act recommended 80% of packaging include the pictorial warnings, however this was reduced to 60% due to pressure form many multinational companies and from some areas of the government itself. In May 2014 Sirisena was elected as one of the Vice Presidents of the World Health Assembly.

Sirisena was declared the winner after receiving 51.28% of all votes cast compared to Rajapaksa's 47.58%. Sirsena was the winner in 12 electoral districts whilst Rajapaksa was victorious in the remaining 10. On the contrary Rajapakse won in 90 electorates while Sirisena managed to win only in 70 electorates. The result was generally seen as a shock. When Rajapaksa called the election in November 2014 he had looked certain to win.

Sirisena's youngest brother, Priyantha Sirisena, died on 28 March 2015 after an axe attack two days earlier in his hometown of Polonnaruwa, 215 kilometres north-east of the capital Colombo. Priyantha was immediately transferred to hospital in a critical condition, where he died from severe head injuries; Sirisena was in China on a state visit at the time.

Sirisena's daughter Chathurika Sirisena launched her first booked title Janadhipathi Thaththa in 2017. This is the first biography written by a daughter of a President of Sri Lanka.