The number of deaths in England and Wales due to the synthetic opioid fentanyl rose by 29% in 2017, Office for National Statistics data shows.
Forms of the drug - used to treat cancer pain - are often imported illegally from Chinese laboratories and sold to users via the dark web.
Deaths from psychoactive substances like spice or mephedrone halved.
Drug policy campaigners called on the government to fund drug treatment and stop criminalising users.
"The UK government has nowhere left to hide. They are responsible for vulnerable people dying in droves," Martin Powell from Transform Drug Policy Foundation said.
He accused politicians of blocking, or refusing to fund, measures proven to save lives in other countries.
Last year heroin and morphine related deaths decreased for the first time since 2012, while cocaine deaths rose.
In total, 3,756 people were recorded as dying from legal and illegal drugs in England and Wales in 2017. The ONS said this figure had "remained stable", with only 12 more deaths than the year previous.
Two thirds of these deaths were accidental, related to drug misuse, the ONS added.
The number of fentanyl deaths increased from 58 in 2016 to 75 in 2017.
The drug has been found mixed with heroin, causing accidental overdoses in users.
The most dangerous version of the opioid, known as carfentanyl, was behind 27 accidental fatalities during the year - the first time it has been recorded in death certificates.
Harry Shapiro, director of DrugWise, said the fentanyl creeping into UK drug supplies was at least 100 times stronger than other class A drugs and that a tiny amount can be fatal.
Meanwhile there were 432 deaths related to cocaine in 2017 - the highest amount ever recorded.
Earlier this year, security minister Ben Wallace warned the UK was "fast becoming the biggest consumer of cocaine in Europe".
England and Wales's rate of 66.1 drug deaths per 1 million, is now more than three times the rate for the EU, Turkey and Norway (according to figures from the European Drug Report).
The latest data showed the north east of England had a significantly higher rate of drug deaths than other regions - 83 per million people - followed by the north west of England and Wales. London had the lowest number of deaths.
In Scotland, drug deaths hit a record high in 2017 and were the worst in Europe, figures revealed last month.
By BBC Home Editor, Mark Easton
Behind the record numbers of deaths from drug poisoning is a row over cuts.
In 2016, the government's official drugs advisory body told ministers the most important way to reduce drug deaths was to protect funding for opioid substitution therapy (OST) - prescribing medicines such as methadone or diamorphine (pharmaceutical heroin) to street heroin users.
More than half the drug deaths last year were from overdoses of opiates, including heroin, and OST is credited with saving hundreds of lives every year.
Responding to the Advisory Council on the Misuse of Drugs recommendations last year, the Home Office accepted the advice on OST "in full", agreeing it "has a widely-recognised and evidenced protective effect in helping to reduce deaths from overdoses".
However, funding for such drug therapy comes from the public health grant distributed to local councils, and that has been cut by hundreds of millions of pounds a year, as part of the government's measures to reduce the deficit.
It is estimated that council spending on adult drug treatment will have fallen 26% since 2014.
Consultant addiction psychiatrist Dr Emily Finch told the Today programme there's been around a 30% loss in funding for drug and alcohol treatment services in the last 5-10 years.
"Generally speaking, the system is less and less fit for purpose," she said.
"Being in treatment protects against deaths."
Prof Fiona Measham who, along with Dr Finch, is a member of the Advisory Council on the Misuse of Drugs, also called for an increase for drug treatment funding.
She said that for many, drug use is a "symptom" of past trauma, abuse or current problems in their lives, rather than "the core of the problem itself".
"The big concern for us in relation to recreational drug users is the five-fold increase in ecstasy deaths and the three-fold increase in cocaine related deaths," she said, adding that these were being caused by higher purity or contaminated substances being sold.