The festival will take place July 29 to August 1 in the city's Grant Park.
The lineup, revealed at 10 a.m., includes Foo Fighters, Post Malone, Miley Cyrus, Tyler the Creator, DaBaby, Journey, Megan Thee Stallion, Roddy Ricch and more.
Tickets went on sale at noon at Lollapalooza.com.
"I'm so excited to finally have some normality back, especially it being an outdoor fest, so it will be so much fun," Rachel Fehrige said. "We can have socially distanced space. It will be a great time."
WATCH | Dave Grohl, Perry Farrell help Chicago mayor announce Lollapalooza's return
In accordance with current local public health guidance, full COVID-19 vaccination or negative COVID-19 test results will be required to attend Lollapalooza 2021.
For patrons who are not fully vaccinated, a negative COVID-19 test result must be obtained within 24 hours of attending Lollapalooza each day.
"To attend Lollapalooza, you either will need to be fully vaccinated or you will need to provide a negative test for every day that you are planning to attend," Chicago Department of Public Health Commissioner Dr. Allison Arwady said. "So the easiest way by far if you want to attend Lollapalooza is to get vaccinated now."
RELATED: Is a vaccination requirement for Lollapalooza legal?
The festival will be at full capacity. In 2019, it drew 400,000 people to the park over four days.
"We've made tremendous progress in containing the spread of COVID-19, with all of our leading metrics stable or on the decline," Dr. Arwady said. "This is a reason to celebrate and why we're able to make this announcement today. To ensure we celebrate safely this summer I encourage everyone to continue to be safe and smart; if you're sick, stay home; wash your hands frequently; wear a mask if you're traveling or using public transit; and most importantly get vaccinated if you haven't already."
WATCH | Chicago city officials discuss Lollapalooza plans
How fans will prove they've been vaccinated is still in the works, but it could involve mobile apps, or showing your vaccination card. Details on the festival entry process will be available in early July, organizers said.
The city hopes it encourages more people to get vaccinated. So far, only 38% of Chicago residents have gotten their shots.
WATCH | Business owners celebrate Lollapalooza's return
The tens of thousands of people flooding the city's center this summer means an influx of long-lost foot traffic for struggling shops and restaurants.
"Huge, huge, like I said, I'm coming in, I'm in for a couple days for business, and just waiting for it to open up," Marchand Boyd said. "And 'll be looking forward to coming back for more events."