During the civil unrest of the 1960s, because of critical opinions voiced against Gheorghe Gheorghiu Dej and the Romanian Communist regime, he was expelled from the University of Bucharest, where he was studying philology. After the Romanian Revolution of 1989, he was a founding member of the Civic Alliance in November 1990, and, after July 1991, began a political career as leader of the minor Civic Alliance Party (PAC), a group that had split from the Alliance to pursue a more political activism, being its candidate for presidency in the 1992 elections; Manolescu subsequently represented the party in the Senate. In 1998, the PAC merged with the National Liberal Party (PNL), and he was a member of the PNL National Council until 2000, when he resigned his position and retreated from political life.
Manolescu has published over 40 volumes on Romanian literature, the most acclaimed being A Critical History of Romanian Literature and a history of Romanian novels, entitled Arca lui Noe (Noah's Ark). His distinction between "doric", "ionic", and "corinthic" novels originated in the traditional orders of the columns of Ancient Greek temples, and covers the distinction between realistic, psychological first person narratives and contemporary, postmodern novels. He has also been the host of the popular Profesiunea mea, cultura ("My Profession Is Culture"), a talk show on cultural matters, aired by Pro TV between 1998 and 2001. Today, he is a professor at the University of Bucharest, from which he has received a Ph.D. in Letters. He is the President of the Romanian Writers' Union, and was designated the Romanian ambassador to UNESCO in 2006.