From 1994 through 1999, he worked for Jean-Georges Vongerichten, where he was eventually named sous chef at Vongerichten's eponymous Jean Georges.
In 1998 he was chef de cuisine at Vongerichten's Prime in The Bellagio, Las Vegas.
In 1999, he left to become the first chef at 71 Clinton Fresh Food.
In April 2003, he opened his 70-seat restaurant, wd~50 (named for the chef's initials and the street address, as well as a pun on WD-40) on Clinton Street on Manhattan's Lower East Side.
In March, 2013, he opened a second restaurant Alder in the East Village.
wd-50 closed 30 November 2014 and Alder closed in August 2015.

Dufresne was a James Beard Foundation nominee for Rising Star Chef of the Year in 2000 and chosen the same year by New York Magazine for their New York Awards.
Food & Wine magazine named him one of 2001 America's Ten Best Chefs award and, in 2006, New York Magazine's Adam Platt placed wd-50 fourth in his list of New York's 101 best restaurants.
He was awarded a star in Michelin's New York City Guide, 2006, 2007, 2008, the first Red Guide for North America, and was nominated for Best Chef New York by the James Beard Foundation.
Among his signature preparations are Pickled Beef Tongue with Fried Mayonnaise and Carrot-Coconut Sunnyside-Up.

In 2006, Dufresne lost to Mario Batali on Iron Chef America.
In 2007, he began making appearances as a judge on Bravo's Top Chef, which includes season 2, season 4, season 5, season 7 and season 12.
He was invited to participate in Top Chef Masters in 2009 where he placed third out of four in the preliminary rounds.
Dufresne also appeared in the final of the United Kingdom version of Masterchef, teaching the eventual winner.
He appeared as himself in the 5th Episode of HBO's Treme alongside Tom Colicchio, Eric Ripert and David Chang.

In 2013, Dufresne won the James Beard Foundation's Best NYC Chef.
It was his 10th nomination and first win.
Unfortunately, Wylie's wd50 restaurant in New York City closed in 2014.

In April 2017, Dufresne, along with head baker Colin Kull and general manager Sharilyn Chavez, took over a pop-up space at the William Vale Hotel in Williamsburg as Du's Donuts & Coffee.
The pop-up grew into a small chain that now has locations in Soho and Brooklyn.
Dufresne's cookbook wd~50, co-written with Peter Meehan, was published in October 2017.
From 1994 through 1999, he worked for Jean-Georges Vongerichten, where he was eventually named sous chef at Vongerichten's eponymous Jean Georges. In 1998 he was chef de cuisine at Vongerichten's Prime in The Bellagio, Las Vegas. In 1999, he left to become the first chef at 71 Clinton Fresh Food. In April 2003, he opened his 70-seat restaurant, wd~50 (named for the chef's initials and the street address, as well as a pun on WD-40) on Clinton Street on Manhattan's Lower East Side. In March, 2013, he opened a second restaurant Alder in the East Village. wd-50 closed 30 November 2014 and Alder closed in August 2015.
Dufresne was a James Beard Foundation nominee for Rising Star Chef of the Year in 2000 and chosen the same year by New York Magazine for their New York Awards. Food & Wine magazine named him one of 2001 America's Ten Best Chefs award and, in 2006, New York Magazine's Adam Platt placed wd-50 fourth in his list of New York's 101 best restaurants. He was awarded a star in Michelin's New York City Guide, 2006, 2007, 2008, the first Red Guide for North America, and was nominated for Best Chef New York by the James Beard Foundation. Among his signature preparations are Pickled Beef Tongue with Fried Mayonnaise and Carrot-Coconut Sunnyside-Up. 
In 2006, Dufresne lost to Mario Batali on Iron Chef America. In 2007, he began making appearances as a judge on Bravo's Top Chef, which includes season 2, season 4, season 5, season 7 and season 12. He was invited to participate in Top Chef Masters in 2009 where he placed third out of four in the preliminary rounds. Dufresne also appeared in the final of the United Kingdom version of Masterchef, teaching the eventual winner. He appeared as himself in the 5th Episode of HBO's Treme alongside Tom Colicchio, Eric Ripert and David Chang.
In 2013, Dufresne won the James Beard Foundation's Best NYC Chef. It was his 10th nomination and first win. Unfortunately, Wylie's wd50 restaurant in New York City closed in 2014.
In April 2017, Dufresne, along with head baker Colin Kull and general manager Sharilyn Chavez, took over a pop-up space at the William Vale Hotel in Williamsburg as Du's Donuts & Coffee. The pop-up grew into a small chain that now has locations in Soho and Brooklyn. Dufresne's cookbook wd~50, co-written with Peter Meehan, was published in October 2017.
Wylie Dufresne