The spike in deaths has coincided with a rapid rise in the abuse of opioid-based prescription painkillers such as oxycontin and hydrocodone.
The CDC said 61% of the deaths involved some type of opioid, including heroin.
Many abusers of painkillers shift to using heroin as it becomes harder to obtain the prescription medications.
"The United States is experiencing an epidemic of drug overdose (poisoning) deaths," the CDC`s report reads.
The report found significant increases in overdoses in 14 states across the country. All regions of the US - including the Northeast and the South - were affected.
Overdose deaths are up in both men and women, in non-Hispanic whites and blacks, and in adults of nearly all ages, the report said.
Rural West Virginia had one of the worse overdose rates in the US. The state rate was 35.5 per 100,000 people; the national rate was about 15 per 100,000.
Many police departments across the country have begun equipping officers with the fact-acting remedy in an effort to save lives.
The health agency has also provided guidelines for general practitioners that urge them to be more cautious about the medications they prescribe for chronic pain.
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