In 1994, Cook moved to New York City, NY and began performing. Two years later, he moved to Los Angeles, where he still lives today. Cook's big comedy break came in 1998 when he appeared on Comedy Central's Premium Blend. This started a relationship between Cook and Comedy Central that has lasted many years. In 2000, Cook did a half-hour special on Comedy Central Presents. Since then his special has won the Comedy Central Stand-up showdown twice in a row. In 2003, Cook released his first CD/DVD, Harmful If Swallowed. The success of the album landed him a recording contract with Comedy Central Records. The album is certified platinum. He released his second CD/DVD in 2005, entitled Retaliation. This album went double platinum and made Cook the first comic in 29 years to have an album at #4 on the Billboard charts. This earned him a place alongside best-selling comedy vets Bill Cosby, George Carlin, and Steve Martin. The success of the album also landed him a comedy performance at the MTV Video Music Awards, and then afterwards he joined Snoop Dogg (who introduced him) in presenting the award for Best New Artist.
On April 15, 2005 Cook performed his first HBO Special entitled Vicious Circle. Inspiration for this comedy was fueled by his late relationship with Amanda Muller. A Junior at SUNY Oneonta. Vicious Circle filmed "in the round" at the TD Banknorth Garden. The same year Cook shot two pilot episodes for his own sitcom, Cooked. The sitcom never got picked up and the two pilot episodes were later released on DVD as the Lost Pilot Episodes. That same year he embarked on a 30-day 20-show college tour called Tourgasm with his long time friends Robert Kelly, Gary Gulman, and Jay Davis. The tour was filmed and was later made into a 9-episode documentary on HBO. On December 3, 2005, Cook hosted Saturday Night Live. It was one of the highest-rated SNLs of the season". He would then go on to host the premiere of season 32 of SNL a year later.
In 2006 Cook headlined for Dave Attell's Insomniac Tour and hosted the 2006 Teen Choice Awards alongside Jessica Simpson. The following year he won the award for Best Comedian. On November 12, 2007, Cook became the second comic to sell out Madison Square Garden. He did two sold out shows in one night. The show was filmed and would later be put onto a DVD to be sold on Cook's third comedy album. Cook won the Big Entertainer Award at the VH1 Big in '06 Awards, and Rolling Stone magazine's Hot Comic of the Year. The following day, November 13, 2007, Cook released his third CD/DVD entitled Rough Around The Edges, which was filmed live at Madison Square Garden in New York City. The Album debuted at #1 on the Billboard Top Comedy Albums chart. During that time, he embarked on his first arena tour.
On April 10, 2007, Cook broke The Laugh Factory's endurance record (previously held by Richard Pryor) by performing on stage for 3 hours and 50 minutes. Dave Chappelle would break the record five days later. On January 1, 2008, Cook broke Chapelle's record, by performing on stage for 7 hours. From May 23, 2008 to May 25, 2008 Cook reunited with Robert Kelly and Al Del Bene for 3 shows at The Coliseum in Caesars Palace. From May 29, 2008 to June 4, 2008, the Trio went to Iraq to perform for the troops. During all of these shows Bene was the Emcee, Kelly was the Feature, and Cook was the headliner. Cook recently finished his fourth album, "ISolated INcident"; it was also a special that aired on Comedy Central on May 17, 2009, with the release of the record following two days later. He kicked off that tour at Mohegan Sun, Uncasville, Connecticut on April 25, 2009. This album will be the last as part of Cook's four record deal with Comedy Central Records. The new album was performed at The Laugh Factory in Hollywood which is considered to be Cook's Home base, where he goes and works on new material. Cook released the DVD version of Isolated Incident on November 17, 2009. It was released in stores and on iTunes. The DVD on the CD/DVD version is Dane talking about his experience doing this DVD special itself.