Greenblatt is one of the founders of new historicism, a set of critical practices that he often refers to as "cultural poetics"; his works have been influential since the early 1980s when he introduced the term.

After graduating from Newton High School, he was educated at Yale University (BA 1964, PhD 1969) and Pembroke College, Cambridge (MPhil 1966).

Greenblatt is considered "a key figure in the shift from literary to cultural poetics and from textual to contextual interpretation in U.S. English departments in the 1980s and 1990s.

[13] After students filed a lawsuit with detailed allegations of Comaroff's actions and the university's failure to respond, Greenblatt was one of several signatories to say that he wished to retract his name from the letter.

[15] Greenblatt's grandparents immigrated to the United States during the early 1890s in order to escape a Czarist Russification plan to conscript young Jewish men into the Russian army.

[17][18] Greenblatt first used the term "New Historicism" in his 1982 introduction to The Power of Forms in the English Renaissance wherein he uses Queen Elizabeth I's "bitter reaction to the revival of Shakespeare's Richard II on the eve of the Essex rebellion" to illustrate the "mutual permeability of the literary and the historical".

[19] As stated by Shakespeare scholar Jonathan Bate, the approach of New Historicism has been "the most influential strand of criticism over the last 25 years, with its view that literary creations are cultural formations shaped by 'the circulation of social energy'.

"[4] When told that several American job advertisements were requesting responses from experts in New Historicism, Greenblatt remembered thinking: "'You've got to be kidding.

I am constantly struck by the strangeness of reading works that seem addressed, personally and intimately, to me, and yet were written by people who crumbled to dust long ago".

[20] Renaissance Self-Fashioning and the introduction to the Norton Shakespeare are regarded as good examples of Greenblatt's application of new historicist practices.

"[23] In particular, as he states in "King Lear and Harsnett's 'Devil-Fiction'," Greenblatt believes that "Shakespeare's self-consciousness is in significant ways bound up with the institutions and the symbology of power it anatomizes".

[25] He is also the co-editor of the anthology's section on Renaissance literature[26] and the general editor of the Norton Shakespeare, "currently his most influential piece of public pedagogy.