The announcement came Friday morning at a graduation ceremony for the latest class of the Chicago Fire Department paramedics.
Nance Holt's new role as fire commissioner is pending City Council approval. She has been a trailblazer with the Chicago Fire Department during her three-decade career.
"At a time when we still have work to do in order to eradicate the scourge of discrimination, racism, and sexism from the firefighter and other professions, Commissioner Nance's appointment couldn't come at a better time," Lightfoot said.
It would be yet another barrier-busting achievement for Nance-Holt, who has overcome personal tragedy to reach the top spot in the Chicago Fire Department.
"It is my honor to stand here before you today, and know that you are my very first class that I would swear in. Thank you Mayor Lightfoot for this opportunity to serve the citizens of Chicago," Nance-Holt said.
WATCH | Annette Nance-Holt poised to make history as 1st Black woman to lead CFD
In 2018, Nance-Holt became the first Black female deputy commissioner. But her 30-year career - in a department trained to deal with tragedies - also brought heartbreak to her own door in 2007 when her son Blair was shot and killed on a CTA bus outside his school.
In response, she co-founded a support group called Purpose Over Pain with Pam Bosley, who lost her son Terrell to gun violence the year before. The two women became dear friends.
"I'm so excited for her because I know the struggles that she went through. It wasn't easy," Bosley said. "I know the pain, I know everything, the things that she went through to get to this point... Blair always wanted her to be the top of the fire department. And now, she's there, and she felt like this week when we was talking, that Blair got her back, you know he's her angel."
Nance-Holt came on board the department four years after the first women joined the ranks. Her nomination is new inspiration to new recruits and seasoned veterans alike.
"A great woman of integrity, an amazing leader committed and dedicated to improving everything that she puts her hand to, and I know that she's going to do a fantastic job, because that's who she is," said Deputy Fire Commissioner Cynthia Herring, who was in the same graduating class as Nance-Holt.
"She can set a great example for all the women to follow," said Agata Ratulowski, a paramedic who graduated Friday.
Nance-Holt would take over a department with a history of racism and sexism. On Friday, she welcomed 42 new members to the department, including 13 women and 15 minorities.
"Graduates, look to Commissioner Nance-Holt's exemplary example of sacrifice and service, even in the face of her own personal pain and tragedy," Lightfoot said. "She is the real deal."
"So what I want to tell you is to always remember that you will be answering the call for someone on their worst day, and they will remember how you made them feel," Nance-Holt said. "Treat everyone with respect and dignity, as if they were your own family member."
Nance-Holt is expected to sail through her confirmation, which could be official as soon as the next city council meeting.