The hospital was chosen because of the care it has provided communities hardest hit by the virus and it's Austin neighborhood location.
State statistics show this area has seen 10,535 COVID-19 cases, the second most in the state.
Black and Brown communities are also suffering historic health care disparities contributing to the pandemic's impact.
"There is no vaccination for racism and we have to deal with that issue and deal with it head on. And that's why we are here," said George Miller, president of Loretto Hospital.
Five health care workers from three different hospitals got inoculated. Chicago Department of Public Health Commissioner Dr. Alison Arwady said five people were getting inoculated at the same time because each vial contains five vaccine doses.
"There is nothing more I wanted for Christmas than a vaccine that looks like this," said Dr. Arwady.
WATCH: 1st COVID-19 vaccines in Chicago administered
Late Monday night, Mayor Lori Lightfoot tweeted photos of the vaccine's arrival in the city. Those doses will be distribute to Chicago's 34 hospitals, including Loretto in the Austin neighborhood, where the COVID-19 death rate is more than 60 percent higher than the citywide average.
"This is truly an incredibly exciting day for all of us," Mayor Lightfoot said. "What we just witnessed is history in the making. It is a milestone in our city's history. I said to each of the pairs of vaccinators and the their patients that they are forever now part of history in the city of Chicago."
CHICAGOLAN VACCINE GUIDE: See COVID-19 vaccine distribution plans for your area
Loretto was the first hospital in the city at 10:30 a.m. to begin inoculating its staff.
Dr. Del Rios is an emergency physician at the University of Illinois Hospital who has been on the front lines, treating COVID-19 patients. She volunteered to get inoculated today for the sake of herself, her family and those in her community hesitant to get vaccinated.
"I thought it was really important that my community see one of their own getting immunized today," said Dr. Rios. "That a Latino willing to step up and to show that this it is safe and effective.
The test positivity rate in Humboldt Park is at 34%. That's about three times the rate of Chicago as a whole according to president of Norwegian American Hospital Jose Sanchez, who himself contracted the virus.
"I spent several days out of work and it was very scary," said Sanchez.
1st COVID-19 vaccine recipient in Chicago speaks after inoculation
The mayor says widespread distribution is still months away and is stressing eq2uity is a major focus of the city's plan.
"It is mandatory not optional, mandatory that you collect the demographic information of the people that are getting vaccinated," said Lightfoot.
Because of the Pfizer vaccine's ultra-cold storage requirement and limited time between thawing and injection, hospitals have carefully crafted rollout plans, intended to prevent waste and any disruptions in patient care.
Pfizer's COVID-19 vaccine: What are the side effects? Who will get it first? Here's what we know
You have to think about the potential for those side effects, so maybe you wouldn't take everybody on your COVID floor and do them all at that same time," said Illinois Department of Public Health Director Dr. Ngozi Ezike.