The new routes are set to launch in April – Birmingham and Manchester to Athens on 14 April and Birmingham to Barcelona on 7 April.
The new services come as the firms prepare to restart their cities programme to a range of destinations in Europe from Monday (7 February), with flights to Rome from Birmingham and Manchester airports.
In February, flights and city breaks to Barcelona (10 February), Budapest (11 February), Krakow (11 February), Prague (11 February), Paris (11 February), Venice (11 February) and Amsterdam (25 February) will also restart.
The return of services to Pisa will commence on 28 March.
Customers can choose from a flight-only option with Jet2.com or an ATOL protected package holiday with Jet2CityBreaks available for £60pp booking deposit.
Steve Heapy, chief executive of Jet2.com and Jet2holidays, said the demand for city breaks has come back "very strongly" as travel starts to "return to normal".
"We are delighted to be resuming our popular city breaks programme to a number of favourite city break destinations," he added.
"Our city breaks programme offers customers and independent travel agents lots of choice and flexibility to choose from for a memorable getaway.
"We are looking ahead with real confidence and optimism, and we expect the return of our cities programme to a number of major city break destinations be very popular, as we know how much customers want to discover their dream city break in 2022."
From Birmingham, twice-weekly services to Budapest will start on 4 March and four-weekly flights and city breaks to Rome are set to resume on 7 February. Twice-weekly services to Krakow and Prague will be available from 11 February, to Venice from 7 April and to Amsterdam from 28 March.
Meanwhile, from Glasgow, twice-weekly services to Rome and Krakow resume on 11 February and to Prague on 3 March.
From Manchester, four-times weekly services resume to Barcelona on 10 February, Budapest on 11 February and Rome on 7 February.
A twice-weekly service which currently operates to Krakow will increase to four-times weekly from 14 February, while services to Nice restart on 14 March, to Prague and Venice 11 February and Pisa 28 March.
Leeds Bradford will see four-times weekly services resume to Barcelona on 4 April and Paris from 11 February. A twice-weekly service to Budapest will restart from 4 March, Rome from 7 April, Krakow and Prague from 11 February and Amsterdam from 25 February.
Newcastle will have two-times weekly routes to Rome, Krakow and Prague recommence on 11 February.
