Born to a Puerto Rican mother and an Irish father, Velez-Mitchell has been on the forefront of many headline news stories during the past decade. She was in the courtroom during the entire child sexual abuse trial against singer Michael Jackson. During the trial, Velez-Mitchell appeared daily on Nancy Grace. She was featured on CNN’s Larry King Live on several occasions, including on the evening of the verdict.

Velez-Mitchell authored the non-fiction book, Secrets Can Be Murder: What America’s Most Sensational Crimes Tell Us About Ourselves, which delves into the secrets unearthed in more than twenty of the most widely covered murder cases of recent times. The book's premise is that, by studying the secrecy and deceit embedded in these tragic scenarios, we can learn to opt for honesty in our own lives and avoid similar outcomes.

In September 2009, Velez-Mitchell released her memoir on addiction recovery titled iWant: My Journey from Addiction and Overconsumption to a Simpler, Honest Life.. "iWant" became a New York Times Best Seller.

In addition to being one of the few openly gay journalists on television, she also has dedicated her time and resources to various charitable and humane causes. She is well known for her animal rights advocacy, is a vegan and an environmentalist. While working at Celebrity Justice, Velez-Mitchell’s reporting on animal cruelty earned that show two Genesis Awards from the Humane Society of the United States. She earned an additional Genesis Award for her show "Issues" in 2010. In January 2010, she was awarded the Ruby Award by Soroptimist International for her "War on Women" coverage on her television show.

She presently resides in Midtown Manhattan with her mother, Anita, who is a former vaudeville performer.