Paymaster General Michael Ellis and Northampton South MP Andrew Lewer could be among more than 100 Conservative casualties, according to figures from Electoral Calculus.
South Northamptonshire MP Dame Andrea Leadsom and Daventry's Chris Heaton-Harris, the government chief whip, would both survive but with vastly reduced majorities.
Electoral Calculus is an experienced predictor of elections and claim to have made the most accurate pre-poll predictions for the UK General Election in 2019.
But Mr Lewer pointed out there is still more than half the current Parliament to run and much can change in more than two years.
He said: “The problem with these types of polling is that they are not much use at predicting election outcomes so far out from election day.
"That’s not to say most politicians do not have a look at them anyway.
"There is still a long way to go until the probable election date in 2024, but I take nothing for granted whatsoever."
These forecasts were made BEFORE local election results in other parts of the country on Thursday (May 5) saw the Tories lose control of key councils including historic swings in parts of London.
But Mr Lewer also pointed out, in a careful assessment on BBC News on Friday (May 6), Britain’s most trusted psephologist John Curtis analysed the local election results and said of the Labour Party: “This is certainly not a local election performance that in any sense indicates a party that is on course for winning a general election.”
Mr Lewer won Northampton South with 51.2 percent of the vote in the 2019 General Election, increasing his majority to 4,697.
But Electoral Calculus’ predictions show Labour would comfortably overturn that with 46.7 percent of the votes.
In Northampton North, Mr Ellis — who has held the seat since 2010 — had a 5,500 majority over Labour's Sally Keeble in 2019, which the Tories won with a landslide 44.7 percent of the national vote.
Electoral Calculus says Mr Ellis’ majority could be wiped out with Labour taking 45.7 percent of votes in the constituency.
Yet their overall predictions for the election result would see Labour leader Sir Kier Starmer fall 11 seats short of an overall majority, based on opinion polls , sampling 12,559 people between April 7 and April 24.
In Daventry, Mr Heaton-Harris' share of the vote would fall from 64.6 percent in 2019 to 47.6 — denting his 26,000 majority — while Dame Andrea, who has held South Northamptonshire since 2010, could see her share of the popular vote drop from 62.4 percent to 45.4 percent.
Forecasts do not take into account boundary changes set to come in before the next General Election is due in 2024.
Up in North Northamptonshire, Wellingborough MP Peter Bone and Philip Hollobone in Kettering would also retain their seats.
But Corby's Tom Pursglove would be another faller with a 16 percent swing to Labour.