Born on Sept. 19, 1966 in Saint James, NY, O’Brien was christened Maria de la Soledad O'Brien. Her first name followed a Spanish tradition of naming a child for "Our Lady of Solitude." A child of bi-racial parents, O’Brien’s father, Edward, was a mechanical engineering professor originally from Australia, while her mother, Estella, was of Black-Cuban heritage, but had immigrated to the States in the 1950s. The couple met at Johns Hopkins University in 1959 and married when an interracial marriage was still illegal in some places in the United States.

O'Brien was raised in Smithtown, a small North Shore town on Long Island, NY. She attended Smithtown High School East before attending Harvard University, obtaining a degree in English and American literature like all her siblings had before her. When the future journalist was 21 years old and a college senior, she left Harvard for her first job in the news business. She returned to Harvard in 2000 while pregnant and completed her degrees.

O'Brien began her career in radio, doing a medical talk show "Second Opinion" and "Health Week in Review" at KISS-FM in Boston in 1989, before working as an associate producer and news writer for “Eyewitness News: First Edition" at WBZ-TV in Boston. From there, she moved to the San Francisco NBC-affiliate, KRON, where she served as a local reporter and bureau chief for three years. In 1991, took a big leap up the ladder when she joined the NBC News department. As a NY-based field producer, O’Brien produced segments for "NBC Nightly News” (1970- ) anchored by Tom Brokaw and “Today” (1952- ). One of her professional highlights included traveling to Cuba to cover Pope John Paul II's historic visit in 1998.

O'Brien began anchoring MSNBC's award-winning technology program "The Site" in 1996. Although short-lived, this hour-long program devoted to technology and the Internet brought her national fame. In 1999, she began anchoring NBC's "Weekend Today," gaining more and more notoriety with each high-profile gig. During that time, she continued to contribute reports for the weekday "Today" show and weekend editions of “NBC Nightly News,” covering such notable stories as John F. Kennedy Jr.'s plane crash and the school shootings in Colorado and Oregon. In 2003, she covered the Space Shuttle Columbia disaster and later anchored NBC's weekend coverage of the war in Iraq.

In July of 2003, CNN snatched O'Brien from NBC, giving her exclusive access as the only broadcast journalist permitted to travel with First Lady Laura Bush on her trip to Moscow. In November of 2004, O'Brien reported from Columbus, OH on the late and contested count of that state’s electoral votes that handed George W. Bush the White House again. In December of 2004, O'Brien was among a handful of CNN anchors sent to Puhket, Thailand to cover the disaster and aftermath of the tsunami that took more than 155,000 lives. For the later coverage, CNN won an Alfred I. duPont Award.

In the summer of 2005, the very busy O'Brien first covered the London terrorism attacks before reporting from the brutal front of America’s Gulf Coast, following the devastation of Hurricane Katrina. As part of CNN’s team covering the latter tragedy, she earned the George Foster Peabody award for the network’s coverage of the natural disaster. Her daily reports on the impact of the hurricane and her in-depth interview with shamed former FEMA chief Michael Brown, drew raves.

In 2006, the awards continued to roll her way. She was awarded the Women of Power award by the National Urban League, also winning a local Emmy for her work as co-host on Discovery Channel's "The Know Zone."

Apart from been named one of People magazine's "50 Most Beautiful People" in 2001 and 2004, O'Brien was also included in Essence magazine's "40 under 40.” The multi-cultural journalist was also named several times to the Irish American magazine’s "Top 100 Irish Americans" and received recognition from the National Association of Minorities with a Cable Vision Award in 2006. An active member of the National Association of Black Journalists and the National Association of Hispanic Journalists, O’Brien continued to wrack up the awards and the respect of fellow broadcast journalists.