The significant level of prior infections is likely to have implications for transmission of the virus in 2021, when there is the potential for Covid-19 vaccines to be deployed across the country, according to the former Food and Drug Administration commissioner.
"We're going to probably have by the end of this year, 30% of the U.S. population infected," Gottlieb said on "Squawk Box." The country has roughly 330 million people. "You look at states like North Dakota and South Dakota, it's probably 30%, 35%. Maybe as high as 50%," he added.
There are roughly 13.4 million confirmed coronavirus infections in America so far this year, according to data compiled by Johns Hopkins University. New daily U.S. cases recently reached single-day records around 200,000.
However, Gottlieb has stressed throughout the pandemic that the actual number of infections is likely higher than that because not everyone who contracts the virus is tested and ultimately diagnosed. In early November, for example, when the country's daily cases were around 121,000, Gottlieb suggested the actual case number was much higher.
"We're probably, at best, diagnosing 1 in 5 cases right now, maybe a little bit less than that, so this is at least half a million cases a day, probably more in terms of actual numbers of infection," Gottlieb said Nov. 6.
The nation's Covid-19 outbreak has intensified since those remarks. The U.S. seven-day average of new coronavirus cases is nearly 162,400, according to a CNBC analysis of Johns Hopkins data. While that's down almost 5% compared with a week ago, inconsistent data reporting due to the Thanksgiving holiday makes the numbers challenging to interpret.
Nonetheless, Gottlieb said the scale of the coronavirus outbreak over the course of 2020 could help limit the spread of the virus early next year if vaccinations begin. Gottlieb is a board member of Pfizer, which was the first company to apply for emergency use authorization with the FDA for its Covid-19 vaccine. His remarks came before Moderna announced its intentions to apply for the same authorization Monday after it announced new data that confirmed its vaccine was more than 94% effective and safe.
"You combine a lot of infection around the country with vaccinating 20% of the population [and] you're getting to levels where this virus is not going to circulate as readily, once you get to those levels of prior immunity," Gottlieb said.
To get to so-called heard immunity, however, health experts estimate between 60% to 80% of a population must be vaccinated or have natural antibodies, allowing them to fight off the virus and significantly curtail its spread in a population.
Earlier this month, Gottlieb urged Americans to take seriously coronavirus precautions around the holiday season, saying the country was facing "really one last surge of infection" and "I do believe 2021 is going to be better." He added, "We have to get through the next two or three months, and so this is going to be, really, a temporary pain."
— CNBC's Nate Rattner contributed to this report.