Quiñones won the Miss Universe 2001 pageant in Bayamon, Puerto Rico in 2001 after a "home town decision". Her win, over Greek supermodel Evelina Papantoniou came on the Miss Universe pageant's 50th anniversary. As Miss Universe, Quiñones resided in New York City for a year, enjoying the benefits that all winners of the pageant receive, including complimentary make-up and haircare, a car, complete wardrobe, professional representation by the Miss Universe Organization, a $60,000 scholarship to a New York City film school, and traveling opportunities.
Since relinquishing the title, Quiñones attended the School for Film and Television's two-year conservatory acting program. Presently an actress, Quiñones has starred in the Spanish version of Nilo Cruz's play Ana en el trópico (Anna in the Tropics) and continues to hone her talent in the United States. For her role in Anna in the Tropics she was nominated and awarded an ACE and Hola Awards. In October 2005 she was selected for the role of Doña Rosita, in a productions of Federico Garcia Lorca's play Doña Rosita la soltera.
Most recently, Quiñones guest-starred in an episode of the WB Network television series Smallville. She played Andrea, a masked avenger who fought crime in Metropolis and invited Clark Kent (Tom Welling) to join her in her adventures. On the heels of her Smallville role, she was also cast in the role of "Rachel", a young fighter pilot in the pilot for the TV series Aquaman which was in development for the CW Television Network. The pilot did not make the Fall 2006 lineup.
In November 2006, Denise led the off-Broadway cast of "Zanahorias" (or "Carrots" in English), a Spanish comedy by Spanish playwright Antonio Zancada. For her role in "Zanahorias" she was nominated and subsequently won the renowned ACE Awards, 2007 edition.
In July 2008, it was announced that Denise will be playing the part of Lara in the upcoming film I Hope They Serve Beer In Hell, based on the book of the same name. On July 24, 2008, producer Tucker Max announced on the film's official production blog that Denise had dropped out due to a scheduling conflict.