One of the main treatments has become useless against the new strain of the sexually transmitted infection.
Twelve cases have been confirmed in Leeds and a further four have been reported in Macclesfield, Oldham and Scunthorpe.
However, there are likely to be more undiagnosed cases.
The strain in this outbreak is able to shrug off the antibiotic azithromycin, which is normally used alongside another drug, ceftriaxone.
Peter Greenhouse, a consultant in sexual health based in Bristol, told the BBC News website: "This azithromycin highly resistant outbreak is the first one that has triggered a national alert.
"It doesn't sound like an awful lot of people, but the implication is there's a lot more of this strain out there and we need to stamp it out as quickly as possible.
"If this becomes the predominant strain in the UK we're in big trouble, so we have to be really meticulous in making sure each of these individuals has all their contacts traced and treated."
The outbreak started in March.
The British Association for Sexual Health and HIV says all cases have been in heterosexuals and some have reported sexual partners from across England.
Dr Jan Clarke, the organisation's president, told the BBC: "It was sufficiently serious to alert our whole national chain of clinics that there is the possibility that we've got a very resistant strain of gonorrhoea.
"We are really skating on thin ice as far as treating gonorrhoea is concerned at the moment."
The disease is caused by the bacterium called Neisseria gonorrhoeae.
The infection is spread by unprotected vaginal, oral and anal sex.
Of those infected, about one in 10 heterosexual men and more than three-quarters of women, and men who have sex with men, have no easily recognisable symptoms.
But symptoms can include a thick green or yellow discharge from sexual organs, pain when urinating and bleeding between periods.
Untreated infection can lead to infertility, pelvic inflammatory disease and can be passed on to a child during pregnancy.
Gonorrhoea is the second most common sexually transmitted infection in England and cases are soaring.
The number of infections increased by 19% from 29,419 in 2013 to 34,958 the following year.
Dr Mike Gent from Public Health England said in a statement: "We can confirm investigations are under way.
"Those affected are being treated with an alternative antibiotic, but the resistance to first-line treatment remains a concern.
"The bacteria that cause gonorrhoea are known to mutate and develop new resistance, so we cannot afford to be complacent."
He urged people to practise safe sex including the use of condoms.
The outbreak in Leeds adds to growing concern that gonorrhoea is becoming untreatable.
In 2011, Japan reported a case of complete resistance to cephalosporin-class antibiotics, which included the main treatment ceftriaxone.
Highly drug-resistant gonorrhoea is spreading in the north of England with an outbreak centred in Leeds, sexual health doctors have told the BBC.