The National Risk Register of Civil Emergencies says such an outbreak could be expected to hit 200,000 people - and two in five of them "might die".
The document also says "high numbers of deaths could also be expected" from other forms of resistant infection.
It warns infection risk could make "much of modern medicine" unsafe.
The Cabinet Office document says the number of infections "complicated" by antimicrobial resistance is expected to "increase markedly over the next 20 years".