Machado was born in Chicago, Illinois, where her family moved to from Puerto Rico. There her parents met and were married. The couple had two children and subsequently divorced. Her mother remarried and had three children. Machado was very active in drama, always participating in her school plays. In 1986, she attended Lane Technical College Prep High School ("Lane Tech") and during her spare time performed with the Latino Chicago Theater Company.
In 1990, she graduated from Lane Tech and moved to New York City. The experience which she had gained as a performer with the Latino Chicago Theater Company helped open the doors for her in that city. Soon, she was offered a job as a professional actress in Los Angeles, California. She moved to Los Angeles and in 1996, Machado landed her first two acting roles. She was cast as "Elsa" in the TV series NYPD Blue episode #311, and she was also cast as "Val Cho" in the movie made for television No One Would Tell.
On June 10, 2001, Machado auditioned for the TV series Six Feet Under and was cast as "Vanessa Diaz", a supporting role character which evolved into a "regular" character in the series. Machado and her castmates were honored with a Screen Actors Guild Award for "Outstanding Performance by an Ensemble in a Drama Series". The series entered its fifth and final season in 2005. Machado has also appeared in the Canadian television series as "Sunny Estrada".
Machado has participated in over 14 films. Amongst her most notable roles so far have been Carmen Rodriguez in She's So Lovely starring John Travolta and Sean Penn, a supporting role in Full Frontal, Isabella Hudson in Final Destination 2 with director David R. Ellis, Agent Herderson in Torque starring Ice Cube, Natalia in Little Fugitive, Teresa in Man Maid starring Sara Rue, Sofia in The Accidental Husband starring Jeffrey Dean Morgan, and FBI Agent Rosie Gomez in "In The Electric Mist".
She has also made appearances on stage, including Neil LaBute's Some Girl(s) at the Geffen Playhouse in Los Angeles. She participated in the productions of Blade to the Heat and Black Butterfly at the Mark Taper Forum in Los Angeles. She was the first replacement for Andrea Burns in Broadway's In the Heights. In 2010 she appeared in the Los Angeles run of Love, Loss and What I Wore.
In 2003, she appeared in the music video for TLC's song "Damaged", the third single from their final studio album 3D, as a young woman trapped in an abusive relationship and unsure of what to do with her life.