There were 4,859 deaths related to drug poisoning registered in 2021.
This equates to 84.4 deaths per million people, the Office for National Statistics (ONS) said.
It is the ninth consecutive annual rise, up 6.2 percent from the previous year, and the highest number since records began in 1993.
The ONS said the overall rising trend over the past decade has been driven primarily by deaths involving opiates, pain-relieving drugs with morphine-like effects, but also those involving other substances such as cocaine.
In the last year there have been “significant” rises from 2020 in deaths involving cocaine, methadone and new psychoactive substances.
Deaths from drug-related poisonings in England and Wales
PA Graphics
The figures cover drug abuse and dependence, fatal accidents, suicides and complications involving controlled and non-controlled drugs, prescription and over-the-counter medications.
Around half of these deaths registered in 2021 will have occurred in previous years due to death registration delays.
The figures show the rates of drug-related deaths have risen 81.1 percent since 2012, when there were 46.6 deaths per million people.
Of the deaths registered last year, 3,809 were due to accidental poisoning while there were 927 instances of intentional self-poisoning.
There were 119 deaths arising from mental and behavioural disorders as a result of drug use, and four deaths following assault by drugs, medicaments and biological substances.
Almost two thirds (3,060) of the deaths were related to drug misuse, and just under half (2,219) involved an opiate.
Some 840 deaths involved cocaine – up 8.1 percent from 2020 and more than seven times the number recorded a decade ago (112 deaths in 2011).
Drug-related deaths in England and Wales have reached a record high
PA Graphics/Press Association Images
There were 663 deaths involving methadone registered in 2021, a 28.5 percent rise from the previous year (516 deaths).
A total of 258 deaths involving new psychoactive substances were registered, up 88.3 percent from the previous year (137 deaths).
People in the North East were more than three times more likely to die due to drugs misuse than people in the East (104.1 deaths per million versus 27.4 deaths per million).
And they were more than three times more likely to die from drug poisoning than people in London (163.4 deaths per million versus 47.6 deaths per million).
Rates of drug misuse deaths continue to be high among Generation X, who were born between the late 1960s and early 1980s.
The charity, Turning Point, called for the Government to continue to invest in “life-saving” health, housing and social care services.
A spokeswoman said: “The pandemic exacerbated an existing public health crisis – however, we are clear that drug deaths are preventable.
“At a time of political uncertainty, these new statistics provide a loud and clear call, whatever your political allegiances.
“The Government’s 10-year drug strategy announced at the end of last year and additional funding coming into services is helping to turn the tide but there is a way to go.”