Before the pandemic, Manchester accounted for more than three million transatlantic passengers a year. The resumption of services will be led by Virgin Atlantic’s Orlando and New York flights on 8 November.
The airport will also be the base for Aer Lingus UK, which has created 153 new jobs with the launch of non-stop flights to the US. Its first US route, to New York, starts on 1 December, followed by Orlando on 11 December.
The airport quotes Aer Lingus’s lead-in Orlando fare at £418, with Virgin’s at £587.
Reid Moody, Aer Lingus chief strategy and planning officer, said: “Aer Lingus is delighted to be re-uniting the UK and the United States via our new base in Manchester.
"We know there is strong demand for direct transatlantic services from the north of England to North America.”
Other resumptions include Virgin’s flight to Atlanta from 2 December and Singapore Airlines to Houston from 1 December.
Karen Smart, Manchester airport managing director, said: “After almost two years with no flights to the USA, it is great to finally look forward to reconnecting the region with some of our most popular and important destinations.”