Jinnah was born Mahomedali Jinnahbhai (Gujarati: મુહમ્મદ અલી જિન્નાભાઈ) in Wazir Mansion, Karachi District, of lower Sindh. Sindh had earlier been conquered by the British and was subsequently grouped with other conquered territories for administrative reasons to form the Bombay Presidency of British India. Although his earliest school records state that he was born on October 20, 1875, Sarojini Naidu, the author of Jinnah's first biography, gives the date as ”December 25, 1876”.

Jinnah was the first child born to Mithibai and Jinnahbhai Poonja. His father, Jinnahbhai (1857–1901), was a prosperous Gujarati merchant who had moved to Sindh from Kathiawar, Gujarat before Jinnah's birth. His grandfather, Poonja Gokuldas Meghji, was a Hindu Bhatia Rajput from Paneli village in Gondal state inKathiawar. Jinnah's ancestors were Hindu Rajputs; his grandfather had converted to Islam. Jinnah's family belonged to the Ismaili Khoja branch of Shi'a Islam, though Jinnah later converted to Twelver Khoja Shia Islam.

The first-born Jinnah was soon joined by six siblings, brothers Ahmad Ali, Bunde Ali, and Rahmat Ali, and sisters Maryam, Fatima and Shireen. Their mother language was Gujarati; in time they also came to speak Kutchi, Sindhi and English.The proper Muslim names of Mr. Jinnah and his siblings, unlike those of his father and grandfather, are the consequence of the family's immigration to the Muslim state of Sindh.

Jinnah was a restless student, he studied at several schools: at the Sindh-Madrasa-tul-Islam in Karachi; briefly at the Gokal Das Tej Primary School in Bombay; and finally at the Christian Missionary Society High School in Karachi, where, at age sixteen, he passed the matriculation examination of the University of Bombay.