Playing a crucial role in the ousting of Governor-General Malik Ghulam Muhammad, Mirza assumed his position in 1955 and was elected as the first President of Pakistan when the first Constitution was promulgated in 1956.

His presidency, however, was marked with political instability which saw his unconstitutional interferences in the civilian administration that led to the dismissal of four prime ministers in a mere two years.

His legacy and image are viewed negatively by some Pakistani historians who believe that Mirza was responsible for weakening democracy and causing political instability in the country.

[11][10][12] As was customary for newly commissioned British Indian Army officers, he was initially attached for a year to the second battalion of the Cameronians (Scottish Rifles).

[10] In spite of hailing from Bengal, his military career was mostly spent in the violent North-West Frontier Province of India, participating in the Waziristan war in 1920.

[15] During his time spent fighting for the British Empire against Pashtun Freedom Fighters in Waziristan, he learnt to speak Pashto fluently for his deployment in the North-West Frontier.

[19] His ability to run the colonial administrative units had brought him to prominence that prompted the British Indian Government to appoint him as the Joint Defence Secretary of India in 1946.

A Muslim Deputy-Commissioner, Janab Iskander Mirza, avowing his traditional loyalty to the British, excelled his masters, beating to death Syed Akbar, a Khudai Khidmatgar.

[21] As Defence Secretary, he oversaw the military efforts in the first war with India in 1947, as well as witnessing the failed secession in Balochistan by Khan of Kalat.

[citation needed] Within a short span of time, the Military Police had control of the state and its commanding officer submitted the report of their course of action to Major General Iskander Mirza in 1954.

[26] Initially, it was Major-General Iftikhar Khan who was promoted to four-star rank and selected to be appointed as the first native commander of the army but died in an airplane crash en route after finishing the senior staff officers' course in the United Kingdom.

[30] On 1 June 1954, Mirza took over the Government of East Bengal from Chief Minister A. K. Fazlul Huq as part of the governor's rule that dismissed the United Front.

[31] After landing at the then Dacca Airport, Mirza sharply announced in the Bengali language to the Pakistan media representatives, that he would not hesitate to use force in order to establish peace in the province, and personally threatening Maulana Bhashani of shooting him.

[30]: 142 Iskander Mirza ruled East Pakistan with an iron fist, having arrested 319–659 political activists in his first week, including Sheikh Mujibur Rahman and Yusuf Ali Chowdhury.

[30] Amid criticism at the public level in Pakistan, Mirza was relieved from the post of the Governorship to East Bengal to Muhammad Shahabuddin in October 1954.

[34] During this time, he had maintained close political ties to the United States's establishment and was backed by Governor-General Sir Malik Ghulam for this post, which Mirza only remained at until 7 August 1955.

[35] During this time, Governor-General Malik Ghulam survived another attack of paralysis that made him unable to talk and walk, seeking treatment in the United Kingdom on a two-month leave.

[36] The Constitution drives the country's system of government towards parliamentarianism, with executive powers vested under the elected Prime Minister while the president served as a ceremonial head of state.

[30] Unable to keep the substantial pressure on Mirza's Republic Party eventually led the Muslim League's successful demand for the resignation of Prime Minister Muhammad Ali on 12 September 1956.

[38] President Mirza demanded the resignation of Prime Minister Suhrawardy and turned down his request to seek a motion of confidence at the National Assembly.

[40] Furthermore, the Republican Party, presided by Prime Minister Sir Feroze Khan, had been under pressure over the electoral reforms issue at the National Assembly.

[40] Upon witnessing these developments, President Mirza ordered the mass mobilization of the military and imposed emergency rule in the country after declaring martial law against his own party's administration led by Prime Minister Feroze Khan by abrogating the writ of the Constitution and dissolving the national and provisional assemblies at midnight on 7/8 October 1958.

[40] Iskander Mirza appointed then-Army Commander of the Pakistan Army, General Ayub Khan, as the Chief Martial Law Administrator (CMLA), which proved his undoing within three weeks.

The martial law would be for the shortest possible duration until the new elections....President Mirza had not envisaged any change in his previous powers; he wanted to retain the ability to maneuver things in keeping with his own whims.

[43] General Ayub Khan came to an understanding that the real political power rested with the support of the military, and within a week of enforcing martial law, President Mirza realized the delicate position he got himself into.

[47] It was reported widely by Pakistani media that despite hailing from a wealthy Nawab and aristocratic family, Mirza lived in poverty in England and his regular income was based on his retirement pension of £3,000 as a former military officer and president.

Mohammad Reza Pahlavi, the Shah of Iran, sent his personal plane to London to bring President Mirza's body to Tehran, where he was given a state funeral.

Hundreds of Iranians, including Prime Minister Abbas Hoveyda, and Pakistani expatriates in Iran bade farewell and offered their prayers.

[10][52][18] Mirza's political ideology reflected secularism, and an image of internationalism, strongly advocating religious separation in state matters.

Iskander Mirza is thus widely held responsible for the instability that brought the active role of Pakistan armed forces into politics.