After returning to India from England, Kaur became interested in the Indian independence movement. His father collaborated closely with leaders of the Indian National Congress, including Gopal Krishna Gokhale, who often visited him. Kaur was attracted by the ideas and vision of Mahatma Gandhi, whom she met in Bombay (Mumbai) in 1919. Kaur worked as Gandhi's secretary for 16 years, and her correspondence was later published in the form of a letter entitled "Letter to Princess Amrit Kaur." After the Jallianwala Bagh massacre at the end of the same year, when British forces shot and killed more than 400 peaceful protesters in Amritsar, Punjab, Kaur became a strong critic of British rule in India. She formally joined the Congress and began active participation in India's independence movement, focusing on bringing social reform. She was against Purdah system and child marriage and was campaigning to end Devadasi system in India.
Kaur co-founded the All India Women's Conference in 1927. He was later appointed its secretary in 1930 and president in 1933. He was jailed in 1930 under the leadership of Mahatma Gandhi for participating in the Dandi March by the British authorities. Gandhi lived in the ashram in 1934 and adopted a lifestyle despite his aristocratic background. British officials appointed him as a member of the Advisory Board of Education, but he resigned from the post in 1942 after joining the Quit India Movement. He was imprisoned by the authorities for his actions during the period of time. Kaur served as the President of the All India Women's Education Fund Association. She was a member of the Executive Committee of Lady Irwin College in New Delhi. He was sent as a member of the Indian delegation to the UNESCO conferences in London and Paris in 1945 and 1946 respectively. He also served as a member of the Board of Trustees of the All India Spinners Association.
After India's independence from colonial rule in August 1947, Kaur was elected from the United Provinces to the Indian Constituent Assembly, the governmental body entrusted to design the Constitution of India. He was also a member of the Sub-Committee on Fundamental Rights and the Sub-Committee on Minorities. After India's independence, Amrit Kaur became part of Jawaharlal Nehru's first cabinet; She was the first woman to get a cabinet rank serving for ten years. He was entrusted with the Ministry of Health. In 1950, she was elected President of the World Health Assembly. As Health Minister, Kaur led a major campaign to fight the spread of malaria in India. She leads the campaign for tuberculosis eradication and was the driving force behind the largest B.C.G vaccination program in the world. From 1957 until her death in 1964, she was a member of the Rajya Sabha. Between 1958 and 1963, Kaur was the president of the All India Motor Transport Congress in Delhi.