Raised by an English nanny, he received his primary education at Bishop's College, Colombo and attended Royal College, Colombo for his secondary education. At Royal College he played for the college cricket team, debuting in the Royal-Thomian series in 1925, and captained the rugby team at the annual "Royal-Trinity Encounter" (which later became known as the Bradby Shield Encounter). Excelling in both studies, Sports and Club and Societies He was the first Chairman/Secretary in Royal College Social Services League in 1921 and he became the head prefect in 1925 and also represented the school in football and boxing; he was also a member of the cadet corps. He would later serve as the Secretary of the Royal College Union.

Jayewardene entered the University College, Colombo (University of London), in 1926 to read English, Latin, Logic and Economics; he attained a distinguished academic record and showed a keen interest in Sports. In 1928 he transferred law by entering Colombo Law College and passed out as an advocate, starting his practice in the unofficial bar, for a brief period. Jayewardene converted from Christianity to Buddhism in his youth.

Jayewardene married Miss Elina Bandara Rupasinghe in 1935, Ravindra "Ravi" Vimal Jayewardene is their only child, he was a pilot in Air Ceylon and served as the Presidential Security Adviser. He was a notable marksmen and the founder of the Special Task Force unit of the Sri Lanka Police .

Jayewardene did not practice law for long. In 1938 he became an Activist in the Ceylon National Congress (CNC), which provided the organizational platform for Ceylon's nationalist movement (the island was officially renamed Sri Lanka in 1972). He became its Joint Secretary in 1939 and in 1940 he was elected to the Colombo Municipal Council from the New Bazaar Ward. He was elected to the colonial legislature, the State Council in 1943 by winning the Kelaniya by-election. During World War II, Jayewardene, along with other nationalists, contacted the Japanese and discussed a rebellion to drive the British from the island.

After joining the United National Party on its formation in 1946, he became Finance Minister in the island’s first Cabinet in 1947. He played a major role in re-admitting Japan to the world community at the San Francisco Conference (see Ceylon's defense of Japan).

Jayewardene's acute intelligence and subtle, often aggressive political skills earned him leading roles in government (1947–1956 and 1965–1970) and in opposition (1956–1965 and 1970–1977). In 1951 Jayewardene was a member of the committee to select a National Anthem for Sri Lanka headed by Sir Edwin Wijeyeratne. The following year he was elected as the President of the Board of Control for Cricket in Ceylon.

By the late 1950s, the UNP struggled to deal with the rising force of the Sinhala-nationalist Sri Lanka Freedom Party. Jayewardene pushed the party to accommodate nationalism and endorse the Sinhala Only Act, which was bitterly opposed by the island's minorities. Throughout the 1960s Jayewardene clashed over this issue with party leader Dudley Senanayake. Jayewardene saw how skilfully the SLFP had played the ethnic card, and felt the UNP should be willing to do the same, even if it meant losing the support of ethnic minorities.

Highly respected in Japan for his call for peace and reconciliation with post-war Japan at the Peace Conference in San Francisco in 1951, a statue of Jayewardene was erected at the Kamakura Temple in the Kanagawa Prefecture in Japan in his honor. In 1988, the J.R Jayewardene Centre was established by the J.R Jayewardene Centre Act No. 77 of 1988 by Parliament at the childhood home of J. R. Jayewardene Dharmapala Mawatha, Colombo. It serves as archive for J.R Jayewardene's personal library and papers as well as papers, records from the Presidential Secretariat and gifts he received in his tenure as President.

As the youngest Finance Minister, in D.S. Senanayake's government, Jayewardene struggled to balance the budget, faced with mounting government expenditures, particularly for rice subsidies. His 1953 proposal to cut the subsidies - on which many poor people depended on for survival - provoked fierce opposition and the 1953 Hartal campaign, and had to be called off.

No government gave serious thought to the development of the tourism industry as an economically viable venture until the United National Party came to power in 1965 and the subject came under the purview of the Minister of State Hon. J. R. Jayewardene.

The new Minister Jayewardene saw tourism as a great industry capable of earning foreign exchange, providing avenues of mass employment, and creating a workforce which commanded high employment potential in the world. He was determined to place this industry on a solid foundation providing it a 'conceptional base and institutional support.' This was necessary to bring dynamism and cohesiveness into an industry, shunned by Leaders in the past, ignored by Investors who were inhibited by the lack of incentive to invest in projects which were uncertain of a satisfactory return. The new Minister Hon. J. R. Jayewardene considered it essential for the government to give that assurance and with this objective in view he tabled the Ceylon Tourist Board Act No 10 of 1966 followed by Ceylon Hotels Corporation Act No 14 of 1966.

In the general election of 1970 the UNP suffered a major defeat, when the SLFP and its newly formed coalition of leftist parties won almost 2/3 of the parliamentary seats. Once again elected to parliament J. R. Jayewardene took over as opposition leader and de facto leader of the UNP due to the ill health of Dudley Senanayake. After Senanayake's death in 1973, Jayewardene succeeded him as UNP leader. He gave the SLFP government his fullest support during the 1971 JVP Insurrection (even though his son was arrested by the police without charges) and in 1972 when the new constitution was enacted proclaiming Ceylon a republic. However he opposed the government in many moves, which he saw as short sighted and damaging for the country's economy in the long run. These included the adaptation of the closed economy and nationalization of many private Business and lands. In 1976 he resigned from his seat in parliament in protest, when the government used its large majority in parliament to extend the duration of the government by two more years at the end of its six-year term without holding a general election or a referendum requesting public approval.

Jayewardene was loath to give up the massive majority he'd won in 1977. He therefore held a referendum to cancel the 1983 parliamentary elections, and allow the 1977 parliament to continue until 1989. He also passed a constitutional amendment barring from Parliament any MP who supported separatism; this effectively eliminated the main opposition party, the Tamil United Liberation Front.

Tapping into growing anger with the SLFP government, Jayewardene led the UNP to a crushing victory in the 1977 election. The UNP won a staggering five-sixths of the seats in parliament—a total that was magnified by the first-past-the-post system, and one of the most lopsided victories ever recorded for a democratic election. Immediately thereafter, he amended the constitution of 1972 to make the presidency an executive post. The provisions of the amendment automatically made the incumbent prime minister—himself—president, and he was sworn in as President on 4 February 1978. He passed a new constitution on 31 August 1978 which came into operation on 7 September of the same year, which granted the President sweeping—and according to some critics, almost dictatorial—powers. He moved the legislative capital from Colombo to Sri Jayawardanapura Kotte.

Jayewardene moved to crack down on the growing activity of Tamil militant groups. He passed the Prevention of Terrorism Act in 1979, giving police sweeping powers of arrest and detention. This only escalated the ethnic tensions. Jayewardene claimed he needed overwhelming power to deal with the militants. He had likely SLFP presidential nominee Sirimavo Bandaranaike stripped of her civic rights and barred from running for office for six years, based her decision in 1976 to extend the life of parliament. This ensured that the SLFP would be unable to field a strong candidate against him in the 1982 election, leaving his path to victory clear. This election was held under the 3rd amendment to the constitution which empowered the President to hold a Presidential Election anytime after the expiration of 4 years of his first term.

Jayewardene said in Daily Telegraph, 11 July 1983," Really if I starve the Tamils out, the Sinhala people will be happy."

The LTTE rejected the accord, as it fell short of even an autonomous state. The provincial councils suggested by India did not have powers to control revenue, policing, or government-sponsored Sinhala settlements in Tamil provinces. Sinhala nationalists were outraged by both the devolution and the presence of foreign troops on Sri Lankan soil. An attempt was made on Jayewardene's life in 1987 as a result of his signing of the accord. Young, deprived Sinhalese soon rose in a revolt, organized by the Janatha Vimukthi Peramuna (JVP) which was eventually put down by the government.

Jayewardene retired from politics in 1989; his successor Ranasinghe Premadasa was formally inaugurated on 2 January 1989.