Yazdi studied pharmacology at the University of Tehran. Then he received a master's degree in philosophy again from the University of Tehran.
After the military coup of 1953, which deposed the government of Mohammad Mossadegh, Yazdi joined the underground National Resistance Movement of Iran, and was active in this organization from 1953 to 1960. This organization opposed to the Shah, Mohammad Reza Pahlavi. Yazdi traveled to the United States in 1961 to continue his education and in the United States, continued his involvement in political activities against the Shah.
Yazdi was co-founder of the Freedom Movement of Iran, Abroad, along with Mostafa Chamran, Ali Shariati, and Sadegh Qotbzadeh in 1961. They were all part of the radical external wing of the group. In 1963, Yazdi, Chamran and Ghotbzadeh went to Egypt and met the authorities to establish an anti-Shah organization in the country, which was later called SAMA, special organization for unity and action. Chamran was chosen as its military head before returning to the United States. In 1966, Yazdi moved the headquarters of SAMA to Beirut. In 1967, he enrolled at Baylor University and received a Ph.D. in biochemistry. Yazdi became a naturalized United States citizen in Houston in 1971.
Yazdi worked as a research assistant of pathology and research instructor of pharmacology at Baylor College of Medicine in Houston until 1977. He also worked at the Veterans Administration Hospital in Houston.
In 1975, Yazdi was tried in absentia in an Iranian military court and condemned to ten years imprisonment, with orders issued for his arrest upon return to Iran. Because of his activities, he was unable to return to Iran and remained in the United States until July 1977. When Ayatollah Khomeini moved to Neauphle-le-Chateau, a Parisian suburb from Iraq in 1978, Yazdi also went to Neauphle-le-Château and began to serve as an advisor to the Ayatollah. He was also his spokesperson in Paris.
In 1978, he joined Ayatollah Khomeini in Paris where the latter had been in exile and became one of his advisors. He translated the reports of Khomeini into English in a press conference on February 3, 1979 in Tehran. He was the deputy prime minister and minister of foreign affairs in the interim government of Mehdi Barargan, until November 6, 1979. Yazdi proposed to celebrate 'Jerusalem Day' and his suggestion was endorsed by Khomeini in August 1979. In May 1980, he was appointed by Khomeini as head of the Kayhan newspaper.
On November 4, 1979, the United States embassy was taken over for a second time, this time by a group calling itself "Students Following the Line of the Imam (i.e. Ayatollah Khomeini)” and led by Mohammad Mousavi Khoeiniha, who had closer ties to certain revolutionary leaders.
As before, Yazdi was asked to go to the embassy and resolve the crisis. He asked and received permission of Khomeini to expel the occupiers, but shortly thereafter found out Khomeini had changed his mind and appeared on state television openly endorsing the takeover of the embassy. The entire cabinet of the interim government, including Yazdi and Prime Minister Mehdi Bazargan, resigned in protest the next day. They stated that they opposed the embassy takeover as “contrary to the national interest of Iran”.
The embassy takeover is considered to have been motivated in part by an internal struggle between various factions within the revolutionary leadership, with Yazdi and Bazargan on one side, and more radical clergy on the other. The embassy attackers, in subsequent statements indicated that one of their primary objectives in the takeover of the United States embassy in November 1979 was to force the resignation of Yazdi, Bazargan, and the entire cabinet.
Among the areas of conflict between the two factions was the behavior of the Revolutionary Courts and the Revolutionary Committees. Yazdi and Bazargan supported a general amnesty for all members of the Shah’s regime, provided that they cease to act against the revolution. They publicly opposed the secret trials and the summary executions carried out by the Revolutionary Courts, led by Ayatollah Sadegh Khalkhaali. Bazargan and other members of the interim government called for fair and open trials for those accused of crimes committed under the Shah’s regime. The radical clerics, on the other hand, stated that the rapid trials and executions were essential to protect the revolution.
After resignation from office, Yazdi and other members of the Freedom Movement of Iran ran in elections for the first post-revolutionary Islamic Consultative Assembly or parliament. Yazdi, Bazargan, and four other members of the Freedom Movement, namely Mostafa Chamran, Ahmad Sadr, Hashem Sabbaghian, and Yadollah Sahabi, were elected. They served in the parliament from 1980 to 1984.
After the Iraqi invasion of Iran in September 1980, Yazdi fully supported the Iranian war effort against the invasion, but opposed the continuation of the war after the Iranian victory in Khorramshahr in 1982. The war continued for an additional six years. During these six years, Yazdi and others in the Freedom Movement issued several open letters to Ayatollah Khomeini opposing the continuation of the war. These letters and other public statements resulted in the firebombing of Yazdi’s residence in Tehran in 1985, and the arrest and imprisonment of several members of the Freedom Movement.
In subsequent elections in Iran for president, parliament, and city councils, Yazdi and other members of the Freedom Movement filed for candidacy but were barred from running by the Guardian Council, because of their opposition to policies and actions of the government.
After the death of Bazargan in January 1995, Yazdi was elected as leader of Freedom Movement of Iran. Under pressure from the revolutionary court prosecutor, Yazdi offered his resignation as FMI Leader on March 20, 2011 to the leadership council of the FMI. By the time of Yazdi's death the leadership council had yet to accept his resignation and Yazdi continued to function as the leader of the Freedom Movement of Iran.
Yazdi was arrested in December 1997 for "desecrating religious sanctities" and was freed on December 26 on bail. Even after his release, he was barred from leaving the country for many years, and was summoned on a regular basis to answer questions before the revolutionary council, with his lawyer, Nobel Prize–winning Shirin Ebadi.
On June 17, 2009, during the 2009 Iranian election protests, it was reported that Yazdi was arrested while undergoing tests at the Tehran hospital according to the Freedom Movement of Iran website. On June 22, Yazdi was released back to the hospital for a medical procedure. On December 28, 2009, Yazdi was arrested again in the wake of renewed protests, according to the Jaras reformist website.
Yazdi and several others were arrested on October 1, 2010 in Isfahan for participating in an "illegal Friday prayer." All others were freed within days. Ibrahim Yazdi remained in "temporary custody" — first in Evin prison and then in a "secure" facility under the control of Iran's security forces until March 2011. He was released in April 2011.
On August 27, 2017, Yazdi died of pancreatic cancer in Izmir, Turkey, where he was under treatment. His body transferred to Iran and was buried in Behesht-e Zahra.