Said was born on 1 November 1935^[15] into a family of Palestinian Christians in the city of Jerusalem, at the time under the British Mandate for Palestine.^[16] His parents were born in the Ottoman Empire: his mother Hilda Said (née Musa) was half Palestinian and half Lebanese, and was raised in the city of Nazareth; and his father Wadie "William" Said was a Jerusalem-based Palestinian businessman.^[17][18] Both Hilda and Wadie were Arab Christians, adhering to Protestantism.^[19][20] During World War I, Wadie served in the American Expeditionary Forces, subsequently earning United States citizenship for himself and his immediate family.^[21][22][23]

In 1919, Wadie and his cousin established a stationery business in Cairo, Egypt.^[18]: 11

Although he was raised Protestant, Said became an agnostic in his later years.^{[24][25][26][27][28]}

Said's childhood was split between Jerusalem and Cairo: he was enrolled in Jerusalem's St. George's School, a British boys' school run by the local Anglican Diocese, but stopped going to his classes when growing intercommunal violence between Palestinian Arabs and Palestinian Jews made it too dangerous for him to continue attending, prompting his family to leave Jerusalem at the onset of the 1947–1949 Palestine War.^[29] By the late 1940s, Said was in Cairo, enrolled at the Cairo branch of Victoria College.^[18]: 179 However, he was expelled in 1951 for troublesome behaviour, though his academic performance was high. Having relocated to the United States, Said attended Northfield Mount Hermon School in Massachusetts—a socially elite, college-prep boarding school where he struggled with social alienation for a year. Nonetheless, he continued to excel academically and achieved the rank of either first (valedictorian) or second (salutatorian) out of a class of 160 students.^[30]

In retrospect, he viewed being sent far from the Middle East as a parental decision much influenced by "the prospects of deracinated people, like us the Palestinians, being so uncertain that it would be best to send me as far away as possible."^[30] The realities of peripatetic life—of interwoven cultures, of feeling out of place, and of homesickness—so affected the schoolboy Edward that themes of dissonance feature in the work and worldview of the academic Said.^[30] At school's end, he had become Edward W. Said, and was fluent in English, French, and Arabic. He graduated with an A.B. in English from Princeton University in 1957 after completing a senior thesis titled "The Moral Vision: André Gide and Graham Greene."^[31] He later received Master of Arts (1960) and Doctor of Philosophy (1964) degrees in English literature from Harvard University.^{[18]: 82–83 [1]}

In 1963, Said joined Columbia University as a member of the English and Comparative Literature faculties, where he taught and worked until 2003. In 1974, he was Visiting Professor of Comparative Literature at Harvard; during the 1975–76 period, he was a Fellow of the Center for Advanced Study in Behavioral Science, at Stanford University. In 1977, he became the Parr Professor of English and Comparative Literature at Columbia University, and subsequently was the Old Dominion Foundation Professor in the Humanities; and in 1979 was Visiting Professor of Humanities at Johns Hopkins University.^[32]

Said also worked as a visiting professor at Yale University, and lectured at more than 200 other universities in North America, Europe, and the Middle East.^[11][33] Editorially, Said served as president of the Modern Language Association, as editor of the Arab Studies Quarterly in the American Academy of Arts and Sciences, on the executive board of International PEN, and was a member of the American Academy of Arts and Letters, the Royal Society of Literature, the Council of Foreign Relations,^[32] and the American Philosophical Society.^[34] In 1993, Said presented the BBC's annual Reith Lectures, a six-lecture series titled Representation of the Intellectual, wherein he examined the role of the public intellectual in contemporary society, which the BBC published in 2011.^[35]

In his work, Said frequently researches the term and concept of the cultural archive, especially in his book Culture and Imperialism (1993). He states the cultural archive is a major site where investments in imperial conquest are developed, and that these archives include "narratives, histories, and travel tales."^[36] Said emphasizes the role of the Western imperial project in the disruption of cultural archives, and theorizes that disciplines such as comparative literature, English, and anthropology can be directly linked to the concept of empire.

Said became an established cultural critic with the book Orientalism (1978), a critique of Orientalism as the source of the false cultural representations in western-eastern relations. The thesis of Orientalism proposes the existence of a "subtle and persistent Eurocentric prejudice against Arabo–Islamic peoples and their culture",^[40] which originates from Western culture's long tradition of false, romanticized images of Asia, in general, and the Middle East in particular. Said wrote that such cultural representations have served as implicit justifications for the colonial and imperial ambitions of the European powers and of the U.S. Likewise, Said denounced the political and the cultural malpractices of the régimes of the ruling Arab élites who he felt internalized the false and romanticized representations of Arabic culture that were created by Anglo–American Orientalists.^[40]

Orientalism proposed that much Western study of Islamic civilization was political intellectualism, meant for the self-affirmation of European identity, rather than objective academic study; thus, the academic field of Oriental studies functioned as a practical method of cultural discrimination and imperialist domination—that is to say, the Western Orientalist knows more about "the Orient" than do "the Orientals."^{[40][41]: 12}

Western Art, Orientalism continues, has misrepresented the Orient with stereotypes since Antiquity, as in the tragedy The Persians (472 BCE), by Aeschylus, where the Greek protagonist falls because he misperceived the true nature of The Orient.^{[41]: 56–57} The European political domination of Asia has biased even the most outwardly objective Western texts about The Orient, to a degree unrecognized by the Western scholars who appropriated for themselves the production of cultural knowledge—the academic work of studying, exploring, and interpreting the languages, histories, and peoples of Asia. Therefore, Orientalist scholarship implies that the colonial subaltern (the colonised people) were incapable of thinking, acting, or speaking for themselves, thus are incapable of writing their own national histories. In such imperial circumstances, the Orientalist scholars of the West wrote the history of the Orient—and so constructed the modern, cultural identities of Asia—from the perspective that the West is the cultural standard to emulate, the norm from which the "exotic and inscrutable" Orientals deviate.^{[41]: 38–41}