Initially Bhulabhai was schooled by his maternal uncle. Later, he studied at the Avabai School in Valsad and the Bharada High School in Bombay from where he matriculated in 1895, standing first in his school. He then joined the Elphinstone College in Bombay from where he graduated in high standing in English Literature and History. He won the Wordsworth Prize and a scholarship for standing first in History and Political Economy. He did his M.A. in English from the University of Bombay. Bhulabhai was appointed Professor of English and History in the Gujarat College, Ahmedabad. While teaching he also studied Law. He married Ichchhaben while still in school. They had only one son, Dhirubhai. Ichchhabhen died of cancer in 1923.

Bhulabhai Desai was enrolled as an advocate at the Bombay High Court in 1905. He made a mark in the legal profession with his thorough knowledge of legal principles, competence, hard work and persuasive handling of cases. His fluent speech, quick grasp, sharp memory and cheerful temperament contributed to his professional success.

At this time, Lawrence Jenkins, Chief Justice of the Bombay High Court took steps toward the "Indianization" of the Bar. Bhulabhai was one of the young and upcoming members of the Bombay Bar. He earned an all India reputation in the field by 1927.

Bhulabhai began his political career in Annie Besant's Home Rule League. He then joined the Liberal Party and remained with it for many years. He opposed the all-white Simon Commission in 1928 by the British Government to report the future of constitutional reforms in India. Bhulabhai considered the Indianization of the army and the navy of far greater importance than that of the civil and the administrative services.

Bhulabhai Desai ably represented the rights of the farmers of Gujarat in the inquiry by the British Government following the Bardoli Satyagraha in 1928. The satyagraha was a No-Tax campaign by the farmers of Gujarat under the leadership of Sardar Vallabhbhai Patel. Gandhiji want the farmers to be represented by the best advocate who was familiar with the conditions and problems of the local peasants. Bhulabhai seemed the logical choice. Bhulabhai's defense of the demands of the farmers made the Government revise the land revenue it charged, return confiscated land to farmers and release prisoners. So pronounced were the effects of the satyagraha and the inquiry that land revenue was reduced in Punjab and the Central Provinces also. 

Bhulabhai Desai formally joined the Congress in 1930 after resigning from the Liberal Party. Convinced about the effectiveness of boycott of foreign goods for furthering the struggle, Bhulabhai formed the Swadeshi Sabha and persuaded 80 textile mills to join in. The Sabha was soon declared illegal and Bhulabhai was arrested in 1932 for his activities in the Sabha. He was treated as an "A" class prisoner with special privileges. While in jail Bhulabhai felt cut off from the outside world. In a letter to his son he wrote, "...in the outer world, my spirits were maintained high," whereas in prison, there is "the stagnant routine and the blank facing of the dead walls." He spent his time reading the Bhagvat Gita and books on various subjects, including Law.

While in jail, Bhulabhai Desai was constantly ill. On his release on health grounds, he went to Europe for treatment. Soon after his return, the Congress Working Committee was reorganized. At Sardar Vallabhbhai Patel's insistence, Bhulabhai was included in the committee.

The Government of India Act of 1935, which allowed provincial autonomy, raised the question whether the Congress should participate in the local legislatures. Bhulabhai among others supported Congress participation and this policy was accepted by the committee. There were many naysayers in the Congress regarding entrance into the legislature. When asked if such a decision went well with India's goal for complete independence, he replied that he was not advocating a "faint- hearted course." He felt that "there was greater heroism in what may appear to be a dreary task than engaging in the heat of a struggle... ."

In November 1934, Bhulabhai Desai was elected to the Central Legislative Assembly from Gujarat. He carried out the difficult task as leader of his party with great skill, dignity and a sense of responsibility. Bhulabhai's first appearance in the Central Legislative Assembly was watched with great anticipation. Eminent Congress leaders were present on the occasion. Under his leadership the party functioned as a team. Bhulabhai entered a debate only when it was necessary to do so. When he spoke he did so with fervor and authority, always avoiding harsh language. When Bhulabhai spoke, there hardly ever was an empty seat in the House. He was not forbidding in the House or outside, yet nobody dared take liberties with him.

He firmly believed that only political and economic interests truly aroused national consciousness of the people of the country. He kept religion away from public since he believed that religion was "a matter between man and God."

World War II raised a whole new set of questions for Indian politics. The British Empire was at war and since India was under British control, India was also at war. The Congress had to decide whether to support the war, remain indifferent to it or launch an all out campaign against the British. The Congress passed the anti-war resolution at its session in Haripura in 1938 which stated that the war was being fought "in the interest of British imperialism" and not in the protection of Democracy. Thus the Congress opposed any preparations being made in India with Indian resources without India's consent.

Bhulabhai Desai considered it important to use the Central Assembly to clarify to the world about the Congress attitude. Bhulabhai addressed the House on November 19, 1940, making a strong plea which read "...unless it is India's war, it is impossible that you will get India's support."

He participated in the Individual Satyagraha Gandhiji started as a protest. He was arrested on December 10, 1940, under the Defense of India Act and sent to Yeravada jail. He was released from prison in September 1941 on grounds of poor health.

By 1945 the political situation in India became very complicated. Tensions between the Congress and Muslim League hung as a dark cloud over India. Gandhiji wanted the Congress and the Muslim League to join hands in Parliament work. Liaqat Ali Khan of the Muslim League and Bhulabhai Desai met several times to hammer out an agreement. Liaqat Ali was ready for a settlement with Congress if the functions and compositions of the proposed Interim Government were clearly stated. Bhulabhai visited Gandhiji at Sevagram in March 1945 to acquaint him with the trend of his talks with Liaqat Ali.

Bhulabhai made a fervent speech in March 1945 to get the House to defeat the war budget. Since most the Congress members were in prison and there was no one to vote down the budget, Sarojini Naidu requested Bhulabhai to attend the budget session to organize the Opposition to defeat the budget. His electrifying speech brought together the Muslim League members as well as the Independents in the House. The budget was defeated by a narrow margin.

The Congress decided to contest elections for the formation of the Constituent Assembly in September 1945. Bhulabhai was not given a ticket in the General Elections because the prevailing impression amongst the Congress brass that he had taken advantage of the Congress Working Committee's imprisonment to gain popularity. Another blow struck when the Desai-Liaqat Ali negotiations were released to the press without reference to Bhulabhai Desai. It was embarrassing for him when Liaqat Ali denied on the floor of the House of any understanding between the two about a "joint course of action." Such propaganda harmed Bhulabhai greatly and his health further deteriorated.

At the end of World War II, the British Government in India decided to try three captured Indian National Army (INA) officers, Shah Nawaz Khan, P. K. Sehgal and G. S. Dhillon of treason against the British Crown. Netaji Subash Chandra Bose, leader of the INA succumbed to injuries when his plane crashed while taking off from Taipei on August 17, 1945. The Congress formed a Defence Committee comprised of 17 advocates including Jawaharlal Nehru, Sir Tej Bahadur Sapru, Sardar Patel and Bhulabhai Desai. The court martial hearing began in October 1945 at the Red Fort. Bhulabhai was the leading counsel for the defense. Undeterred by bad health, Bhulabhai made the most effective argument in defense of the charged soldiers. He worked for three months at a stretch. His defense speech, lasting for several days, was made without the help of any notings. He based his arguments on the principles of International Law. He argued that International Law entitled the accused to take up arms to liberate their country under the order of the Provisional Government which Netaji had established and which had the recognition of a few sovereign governments. As such, he said, they could not be charged for the offence under the Indian Penal Code. He "attained the highest watermark of his legal career" during the trial.

The British, on prestige, pronounced the three INA officers guilty and sentenced them to transportation for life. But the mass upsurge following the trial together with the mutiny of the Royal Navy and Air Force, forced the British to set the three officers free.

The nation was overwhelmed with Desai's historic defense. He was given a hero's welcome on his return to Bombay.

Bhulabhai Desai died on May 6, 1946. His immense wealth led to the creation of the Bhulabhai Memorial Institute.