Nancy Grace was born in Macon, Georgia, the youngest of three children, to factory worker Elizabeth Grace and Mac Grace, a freight agent for Southern Railway. Her older siblings are brother Mac Jr. and sister Ginny. The Graces are longtime members of Macon's Liberty United Methodist Church, where Elizabeth plays the organ and Mac Sr. was once a Sunday School teacher. Grace graduated from Macon's Windsor Academy in 1977.

After leaving the Fulton County prosecutors' office, Grace was approached by and accepted an offer from Court TV founder Steven Brill to do a legal commentary show alongside Johnnie Cochran. When Cochran left the show, Grace was moved to a solo trial coverage show on Court TV, she hosted Trial Heat from 1996-2004, then Closing Arguments from 2004-2007, replacing Lisa Bloom and James Curtis, both of whom were hosting Trial Heat at that point.  In 2005, she began hosting a regular primetime legal analysis show called Nancy Grace on CNN Headline News (now HLN) in addition to her Court TV show. On May 9, 2007, Grace announced that she would be leaving Court TV to focus more on her CNN Headline News Program and charity work. She did her last show on Court TV on June 19, 2007.  Grace has a distinctive interviewing style mixing vocal questions with multimedia stats displays. The Foundation of American Women in Radio & Television has presented Nancy Grace with two Gracie Awards for her Court TV show.  Grace had been covering the Casey Anthony story for years. After the controversial verdict finding Casey Anthony not guilty, her show on HLN had its highest ratings ever in the 8 p.m. and 9 p.m. hour slots on Tuesday, July 5, 2011.  Grace also hosted Swift Justice with Nancy Grace premiering September 13, 2010, and running until May 2011. Grace left the show due to productions moving from Atlanta to Los Angeles. In September 2011, Judge Jackie Glass, who is known for presiding over the O. J. Simpson robbery case, took over Grace's place. The show continued for one more season and ceased production in 2012.

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