The region that forms today's Karen State was part of successive Burmese kingdoms, since the formation of the Bagan Empire in mid-11th century.

They refused to sign the Panglong Agreement of February 1947, which was the basis for the 1947 Constitution of Burma, and boycotted the pre-independence elections of April 1947.

In January 2012, Myanmar's military-backed civilian government signed a ceasefire deal with the KNU in Hpa-an, the capital of eastern Kayin State.

Aung Min, the Railway Minister, and General Saw Chee Tik of the KNU led the peace talks.

[9] Minority religious communities include Christians (9.5%), Muslims (4.6%), Hindus (0.6%), and animists (0.1%) who collectively comprise the remainder of Kayin State's population.

After the signing of the preliminary ceasefire between the KNU and the Myanmar government in 2012, the number of visitors to Kayin State increased largely.

According to Thailand's Chamber of Commerce, the monthly trade between the two countries in 2015 through the Mae Sot to Myawaddy crossing was worth over 3 billion baht (about 90 million US dollars).

[14] In 2016, the government announced a strategy to attract domestic and foreign investors to the Hpa-An industrial zone.

The Kayin State government in conjunction with a Japanese company has been trying to carry out a feasibility survey for an 1800-megawatt coal-fired power plant to fulfil the need of electricity supply.

On the other hand, community members and local environmental groups have raised concerns about the potential impacts from coal plant emissions.

In 2015, the Asian Development Bank (ADB) approved a $100 million loan to improve a 66.4 km section of road connecting the towns of Eindu and Kawkareik in Kayin state, the missing link of the Greater Mekong Subregion (GMS) East-West Corridor.

It is especially a problem in Karen State where constant fighting between the government and insurgents for over 60 years has produced thousands of refugees and internally displaced people.

Although health care is nominally free, in reality, patients have to pay for medicine and treatment, even in public clinics and hospitals.

In general, the health care infrastructure outside of Yangon and Mandalay is poor but is especially worse in conflict ridden areas like Karen State.