He originally garnered fame as a member of boy band Menudo in the 1980s. Afterwards he moved to California and formed the band Maggie's Dream, which split after only one album, allowing him to resume his solo career. Draco has released numerous studio and experimental albums, and has composed and produced multiple songs for Ednita Nazario, Julio Iglesias and former Menudo band-mate, Ricky Martin.

In 1988 he made his motion picture debut in the motion picture Salsa, which was a big hit in Puerto Rico. During the filming of the movie, he met actress Angela Alvarado who would later become his wife.

Rosa has been highly influenced by the works of Bob Dylan, Miles Davis, Iggy Pop, Jimi Hendrix, Johnny Cash, Luis Alberto Spinetta, The Doors, Camarón de la Isla, Caetano Veloso and Glenn Danzig. In 1996 he released the Latino alternative rock album Vagabundo produced by Phil Manzanera.

In the 1990's he helped launch Ricky Martin's musical career into a new global setting by writing and producing various of his hottest singles including María, La Vida Loca, La Copa de La Vida, She Bangs, and Shake Your Bon-Bon. Rosa toured with Lenny Kravitz during the summer of 2004 to promote his concept album Mad Love.

Draco yet again honored his roots in 2009 with the release of "Amor Vincit Omnia" (Love Conquers All). A collection of songs with a heavy influence of Puerto Rican folk music. The critically acclaimed album received a 2010 Grammy nomination for "Best Latin Rock Alternative Album" and received the Rock Record of the Year at Premios Lo Nuestro 2011 with two other nominations for Artist and Song of the Year. A successful tour followed culminating in Rock in Rio in Madrid, where Draco shared the main stage with Jane's Addiction and Rage Against the Machine.

In April 2011, Draco was diagnosed with a non-hodgkin lymphoma cancer near his liver. He underwent alternative and traditional treatment in Texas and California. This kept Draco in a hiatus for almost a year until his return in March 2012, when he started recording his latest album with "Vida", and gave a concert with Juan Luis Guerra and Rubén Blades at the Coliseo de Puerto Rico Jose Miguel Agrelot. In December 31st 2012, he was declared cancer-free.

On April 23, 2013, previous to the 2013 Billboard Latin Music Awards, Draco received the first Premio Conquistador given by the Latin Songwriters Hall of Fame at the New World Center in Miami and presented to him by Rubén Blades. After the presentation of the award, Draco and Rubén shared the stage to perform a duet of "El Tiempo Va", included in "Vida". Two days after, Draco and Mexican band Maná performed "Penélope" together at the 2013 Billboard Latin Music Awards, held at the BankUnited Center in Miami on April 25, 2013.

Draco will return to the stage on December 6, 2013 at the Coliseo de Puerto Rico José Miguel Agrelot with a concert entitled "Draco Rosa & Friends". Many artists participating in "Vida" are expected to perform alongside Draco.

Draco owns a recording studio, an independent music label and a multimedia company under the name of Phantom Vox. He also owns Hacienda Horizonte in the mountains of Utuado, Puerto Rico where he has shot two music videos of his Amor Vincit Omnia album: "Paraíso Prometido", and "Reza Por Mí". Aside from the many different projects going on at the farm, Draco has created his own line of rum, Ron Vagabundo; a brand of locally grown coffee, Café Horizonte and a spectacular line of clothing, Vagabundo Clothing.

Puerto Rico's Chamber of Commerce awarded Draco with the Zenit award as Businessman of the Year.