Das started practicing in the Calcutta High court and had the opportunity to defend national workers like Bipin Chandra Pal and Arvinda Ghosh. The case against Arvinda Ghosh came to be known as the Alipore Bomb Conspiracy. Two attempts on the life of the Chief Presidency Magistrate of Calcutta, Mr. Kingsford, were made because he was ruthless while handing out punishments. The first attempt through a mail bomb was a failure. The second attempt was made by Khudiram Bose and Prafulla Chaki. The attempt resulted in the death of 2 innocent English women but Lord Kingsford escaped. Prafulla committed suicide and Khudiram was captured and sentenced to death. A witch hunt ensued and A. Ghosh was labelled the master-mind behind the blasts by the British Government. Nobody was ready to defend Ghosh except Chittranjan Das. The entire trial lasted for 126 days, 200 witnesses were examined, 4000 paper exhibits and 500 material exhibits in the form of bombs and explosives were filed in the case. Das's concluding statements alone lasted for 9 days. Arvinda Ghosh was acquitted. Das accepted no fee for defending Ghosh; in fact he incurred a heavy loss of Rs. 15,000 by the time the case was complete.
Besides being an astute lawyer, Das was a literary man. He has works like Mala and Antaryami (poems expressing religious spirit and devotion), and Kishore Kishori (poem expressing the eternal love between Lord Krishna and Radha). Along with Arvinda Ghosh, he founded the famous journal Bande Mataram. He was also the editor in chief of the journal Forward, a mouthpiece of the Swaraj party.
Das was moved by Gandhiji's call for non-violent resistance to the British Government. The Indian Reforms Act, also known as the Montford Reforms were passed in 1919 in Britain. The reforms were aimed at achieving a responsible government in India. Das moved a resolution declaring the reforms "inadequate, unsatisfactory and disappointing." He appealed to the Government to make a conscientious effort for setting up a more responsible government in India. The Congress accepted Das's resolution with a few amendments. A sub-committee recommended a boycott of educational institutions, law courts and legislative councils. Das believed that most effective way to gain freedom was to fight the British from without and within. He favored the boycott of the schools and courts but opposed the boycott of legislative councils.
Das declared that he would give up his practice to set an example for his people. Das played an important role in the boycott of the arrival of Prince of Wales in Calcutta on November 17, 1920. When the Prince stepped into the city he found it deserted. Das did his best to keep the boycott complete and peaceful. He organized the Congress Volunteers Corps for effectively implementing Congress programs. He enrolled one crore volunteers to raise Rs 1 crore for the Tilak Swaraj Memorial Fund. The volunteers were involved in picketing Government offices, shops selling foreign goods, liquor shops. They were also involved in selling khaddar. This led to an unprecedented mass awakening.
The fallout of the boycott of colleges resulted in many students with no educational institution to go to. Das setup the Bengal National College to fulfill the demands of the students. In December 1921 Das was arrested. Getting into the police car Das told the crowd, "Men and women of India. This is my message to you. Victory is in sight if you are prepared to win it through suffering." Conches were blown and flowers showered on Deshbandhu (literally: friend of the nation) as he was fondly called for the sacrifices he made for the freedom struggle, as the police car started. Deshbandhu was first imprisoned in the Presidency Jail and was moved to the Central Jail where many of his followers were imprisoned. Das was released the following year.
Deshbandhu, along with Motilal Nehru, founded the Swaraj Party in 1923 for maintaining of continued participation in legislative councils. The party was soon recognized as the parliamentary wing of the Congress. In Bengal many of the candidates fielded by the Swaraj Party were elected to office. The Governor invited Deshbandhu to form a government but he declined. The party came to be a powerful opposition in the Bengal Legislative Council and inflicted defeats on three ministries.
The Calcutta Municipal Act of 1923 was a major landmark in the history of local self-government in India. The Swarajists were elected to the Calcutta Corporation in a majority in 1924. Deshbandhu was elected mayor and Subash Chandra Bose was appointed Chief Executive Officer. Greater efficiency was brought to the administration and many welfare projects were implemented. After giving up his legal practice Deshbandhu went from one of the richest men in Calcutta to one of the poorest. His liabilities amounted to one lakh rupees. The only asset he had was his huge building in Calcutta which he wanted to gift to the nation. Deshbandhu set up a fund, which was later made the Deshbandhu Memorial Fund through Gandhiji's intervention to clear his liabilities, build a temple, establish an orphanage and provide education to the masses. establish an orphanage and provide education to the masses. The total amount collected by the fund amounted to eight lakh rupees. Deshbandhu's home was converted to a hospital for women and is called Chittranjan Seva Sadan.
The struggle with the Government became more intense on account of the legalization of the oppressive Bengal Ordinance which authorized arrest of individuals suspected of terrorism without probable cause. Das had returned with a high fever from the Belgaum Congress session of 1925. When he heard that the ordinance was to be legalized on January 7, 1925, Deshbandhu declared from his sickbed, "The Black Bill is coming up for discussion. I must attend at any cost and oppose it." He was taken to the Council on a stretcher attended by two doctors. The bill was defeated. On June 16, 1925, Deshbandhu's condition worsened. He died while resting in Darjeeling. On Deshbandhu's death, Subash Chandra Bose said, "The death of Deshbandhu... was for India a national calamity... ."