From 1999 to 2006, de Zegher served as executive director, chief curator, and editor at The Drawing Center, New York. Under her seven-year leadership, the center presented more than sixty historical and contemporary shows, expanded its archive and lecture program, and created a viewing program that invited artists to drawing-based public art projects and performances. From 2003 to 2005, she led negotiations to move The Drawing Center, based in SoHo, to Ground Zero as part of the plans to share a building with a proposed International Freedom Center. The project was part of the memorial for the victims, and a museum intended to draw attention to battles for freedom throughout history planned in the immediate aftermath of the attacks and destruction of the World Trade Center. After a power struggle set off by the move to Ground Zero, de Zegher resigned in March 2006. De Zegher's curatorial projects at The Drawing Center include "Eva Hesse Drawing" jointly curated with Elisabeth Sussman and "Joelle Tuerlinckx's Drawing Inventory" both in 2006; "Persistent Vestiges: Drawing from the American Vietnam War", and "3 x Abstraction: New Methods of Drawing by Hilma af Klint, Emma Kunz, and Agnes Martin", "Richard Tuttle: It's a Room for 3 People" in 2005; "Ocean Flowers: Impressions from Nature" with Carol Armstrong (2003-2004); "Giuseppe Penone: The Imprint of Drawing" (2004); "The Stage of Drawing: Gesture and Act. Selected from the Tate Collection" (2003); "Anna Maria Maiolino: A Life Line/Vida Afora" (2002); "Bracha Lichtenberg Ettinger: Eurydice Series", and "Between Street and Mirror: The Drawings of James Ensor" both in 2001; "Untitled Passages by Henri Michaux" co-curated with Florian Rodari and "The Prinzhorn Collection: Traces Upon the Wunderblock" in collaboration with Inge Jadi and Laurent Busine both in 2000.