Holt followed in the career footsteps of Max Robinson, an ABC News evening co-anchor, and became the first Black male solo anchor for a major network newscast.

Holt's maternal grandfather Canute DeRozario was of Anglo-Indian descent from Spanish Town, and was one of 14 children born to an Indian father from Calcutta, and an English-born White Jamaican mother.

Holt was introduced to broadcasting by his older brother, a disc jockey at a local radio station in Anchorage, Alaska.

[19] In 2012, Holt told American Profile news magazine: "My first on-air job was actually as a disc jockey at a Country and Western station.

Holt not only worked at the anchor desk but also reported extensively from troubled spots around the world, including Iraq, Northern Ireland, Somalia, El Salvador and Haiti.

He moderated a presidential debate in 2016, and interviewed President Donald Trump in 2017, where fellow journalists said that he asked tough but appropriate questions.

In 2015, Williams was suspended for reportedly exaggerating a story about the Iraq War, and Holt permanently replaced him as NBC Nightly News anchor.

[28] Prior to the debate, presidential candidate Donald Trump said that this was "a very unfair system" because "Lester is a Democrat" (Holt was at the time a registered Republican.

[30][31] The Washington Post said "Kudos to Holt" for making it clear that stop and frisk was ruled unconstitutional in New York, when Trump said it wasn't.

[37][38] In 2022, Holt announced the death of Queen Elizabeth II in an NBC News Special Report,[39] and in 2023, he interviewed Ebrahim Raisi, president of Iran.

Holt announced the 2006, 2007, and 2008 Westminster Kennel Club Dog Show for the USA Network, and was featured in Making Music magazine.

[21] Stefan Holt graduated in 2009 from Pepperdine University and was the morning news anchor at NBC-owned WMAQ-TV in Chicago.