The provisional data said heart disease claimed about 690,000 lives, all forms of cancer claimed just over 598,000 lives and COVID-19 was responsible for more than 375,000 American deaths last year.
The CDC said of the 378,048 death certificates it received tied to coronavirus in 2020, COVID-19 was listed as the sole cause of death in 5.5% of them. Of the other death certificates listing COVID-19, 97% also listed "a plausible chain-of-event condition" -- for example pneumonia or respiratory failure. Another main contributor was hypertension, diabetes, or both, according to the report.
In late February, the U.S. surpassed 500,000 COVID deaths, according to data from Johns Hopkins University.
COVID-19 displaced suicide as one of the top 10 causes of death. Overall, the year's death rate was up nearly 16% compared to the previous year, the report said.
The news was announced just before the White House COVID-19 Response Team addressed the nation to give an update on current efforts against the virus. The 11:15 a.m. Eastern briefing included top infection disease expert Dr. Anthony Fauci, CDC Director Dr. Rochelle Walensky and Andy Slavitt, White House Senior Advisor for COVID-19 Response.
The CDC also said Wednesday the COVID-19 death rates were highest among Hispanics.
On Monday, Dr. Walensky pleaded with Americans to "sound the alarm" and work together to prevent a possible fourth surge of COVID-19.
"We have so much to look forward to, so much promise and potential of where we are and so much reason for hope, but right now I'm scared," CDC Director Dr. Rochelle Walensky described during Monday's White House COVID-19 briefing.
Walensky explained that the seven-day average for new coronavirus cases in the U.S. is up 10%, hospitalizations are rising and COVID-related deaths have increased to an average of 1,000 per day.
The CDC said the findings in its newest report support the "accuracy of COVID-19 mortality surveillance in the United States using official death certificates." It added that proper documentation on death certificate diagnosis is essential for public records.
The coronavirus, which was first directed in the United States in January of 2020, is blamed for the deaths of more than 551,000, according to a tally from Johns Hopkins University.
The Associated Press contributed to this report.