Lemon was born in West Baton Rouge, Louisiana. He earned a broadcast journalism degree from Brooklyn College. He also attended Louisiana State University.

Prior to joining the CNN, Lemon co-anchored at NBC-owned station WMAQ-TV in Chicago during the 5 p.m. newscast. He joined the station in August 2003 as an anchor and reporter after working in New York as a correspondent for NBC News, The Today Show and NBC Nightly News. In addition to his reporting in New York, Lemon was an anchor on Weekend Today and on MSNBC.

In addition to NBC5 and NBC News, Don worked as a weekend anchor and a general assignment reporter for WCAU-TV, the NBC-owned station in Philadelphia. Before that, a general assignment and investigative reporter for KTVI-TV in St. Louis, and as a reporter for Birmingham, Alabama's WBRC-TV. While still in college, he began his career at WNYW in New York as a news assistant.

Lemon conducted a 2010 phone interview with U.S. Senate candidate Alvin Greene. Lemon reportedly remarked afterwards that it was "one of the most bizarre" interviews he's given.

During an on-air interview with members of Bishop Eddie Long's congregation on September 25, 2010, Lemon stunned viewers by announcing that he was a victim of sex abuse as a child, and it wasn't until he was thirty that he informed his own mother.