In 2000, Posen received a big break after a dress he made for Naomi Campbell changed hands several times among several fashion insiders, including actress Paz de la Huerta. He is famously well-connected and has called Stella Schnabe his muse.
Through Interview magazine Editor-in-Chief Ingrid Sischy, Posen met his future publicist and event producer Ed Filipowski of KCD, who offered to represent him for free
Upon returning to New York in 2001, Posen set up an atelier in his parents' living room, while they gave him a USD$15 allowance.
In October of the same year, he was chosen to present a capsule collection as part of GenArt's Fresh Faces in Fashion New York 2001. He received a grant for $20,000
After his first runway show in 2001, Posen was courted by fashion titans Yves Carcelle, president of LVMH Fashion Group; Sidney Toledano, CEO and director of Christian Dior S.A.; and Domenico De Sole, president and CEO of Gucci Group NV. Following the success of this presentation, Posen established his design studio in Tribeca.
His awards include the Council of Fashion Designers of America's 2004 Swarovski's Perry Ellis Award for Womenswear. Posen has become a favorite of Natalie Portman, Rihanna, Amanda Seyfried, Kate Winslet, Claire Danes, Cameron Diaz, Jennifer Lopez, Mischa Barton, Beyoncé Knowles and others.
In 2004, high-end urban fashion brand Sean John made an investment deal with Posen. Ashley Olsen interned with Posen in 2005 while a student at The Gallatin School of Individualized Study, an undergraduate college within New York University.
In April 2008, Posen's capsule collection created in collaboration with Target, Zac Posen for Target, was released in 75 stores in Australia. A preview of the collection was shown during March's L'Oreal Melbourne Fashion Festival.
At the 2012 Academy Awards, Glenn Close wore a Posen gown on the red carpet, as did both Reese Witherspoon and Naomi Watts at the 2013 Golden Globe Awards. Other notables who have worn Posen creations on red carpets include Uma Thurman at the 2013 Met Ball); Sofia Vergara at the 2014 Golden Globes; Anna Chlumsky at the 2014 Emmy Awards; and Rita Ora at the 2014 AMA Awards.
On December 18, 2012, Posen was announced as an official judge of Project Runway Season 11 on Lifetime Television.
In February 2014, Posen partnered with another major retailer, David's Bridal, to create Truly Zac Posen, a line of affordable bridal gowns. The line was Posen's first official bridal collection. Also in 2014, he was named Creative Director for Brooks Brothers, tapped to modernize their signature women's clothing and accessories line. In 2014, he introduced a more casual Pre-Fall 2015 Trunk Show collection.
In recent collaborations, Posen was selected to redesign the uniforms for Delta Air Lines 60,000 employees. These uniforms are set to appear on Delta Air Lines staff members, from flight attendants to customer service, in 2017.
Posen lives in the New York neighborhood of SoHo, with his boyfriend, Christopher Niquet and their three dogs. Posen is of Jewish descent, with immigrant ancestors from Russia, Poland, and Romania.