Lori Lightfoot won each of the city's 50 wards in a stunning victory, beating political veteran and Cook County board president Toni Preckwinkle - who is also an African-American woman.
The former federal prosecutor pledged to address violence in the US city and make it a "place where your zip code doesn't determine your destiny".
Ms Lightfoot, 56, who has never before been elected to public office, will be the second woman to lead Chicago.
There are currently seven other black women serving as mayors in major US cities.
She has described herself as "an out and proud black lesbian" and said her campaign created a "movement for change".
The 56-year-old will succeed mayor Rahm Emanuel, an ex-White House chief of staff to Barack Obama, who decided not to run for a third term.
Ms Lightfoot said: "We can and we will build trust between our people and our brave police officers so that the communities and police trust each other, not fear each other.
"We can and we will break this city's endless cycle of corruption... and never again, never ever allow politicians to profit from elected positions."
Ms Lightfoot will be sworn in on 20 May.
In 2016, Chicago recorded 762 homicides - the highest number in two decades - but the killings dropped to 550 in 2018.
US media reports there has been a decrease in homicides in the city compared to the same period last year, with murders down 30% in the first three months of the year.