Commons Leader Penny Mordaunt said having such a limit as the default for many roads is “crazy”, after acknowledging there are circumstances where 20mph is a good idea.
Ms Mordaunt went on to accuse Labour of “punishing” motorists.
The Welsh Government has said that cutting the speed from 30mph to 20mph on residential roads would protect lives and save the NHS in Wales £92 million a year.
But it will mean many communities on the Shropshire-Mid Wales border having two speed limits to contend with.
Most roads in Wales that are currently 30mph will become 20mph, although councils have discretion to impose exemptions.
The change will be implemented from September 17 and First Minister Mark Drakeford said it is the “right thing to do”, citing a fall in urban road deaths in Spain after it made a similar change in 2019.
Speaking in the House of Commons, Conservative MP Virginia Crosbie (Ynys Mon) said: “The Labour Government in Cardiff supported by Plaid Cymru will be introducing a blanket 20mph speed restriction in built-up areas across Wales from September 17.
“In many places - outside schools, outside hospitals - 20mph is appropriate.
“Does the Leader of the House agree with many of my Ynys Mon constituents that this blanket approach will impact main roads and impact the Welsh economy?
“And will she make time for a debate on how we should be supporting the Welsh economy, not punishing it?”
Ms Mordaunt replied: “This is absolutely insane even by the standards of Labour’s Welsh Government.
“They have ignored businesses and they have ignored the public. They are pushing ahead with this scheme despite huge opposition to it and I think the latest estimate is it will cost the Welsh economy £4.5 billion.
“But more disturbingly it is going to increase individuals’ fuel bills considerably and actually be harmful to the environment.
“(Ms Crosbie) is right, there are circumstances where of course 20mph speed limits are a good idea, but having them as the default for many roads is crazy.
“Instead of punishing motorists, Labour should be focusing on fixing public transport, in particular the trains.”
Ms Mordaunt added: “This situation is what the Labour Party refers to as their blueprint for governing Britain.”
The Welsh Government, responding to why people say the change will cost the economy £4.5 billion, writes on its website: “Our assessment shows that reducing speeds to 20mph can result in an average increase of one minute per journey, nine lives saved and 98 serious injuries prevented each year.
“Before the law was passed, we produced an impact assessment that considered all the potential costs. This was included in the explanatory memorandum.
“It included the costs of any delays to travel time. The method used is now under academic debate for its effectiveness when calculating small delays.
“So the estimated cost to the economy of £4.5 billion over 30 years may not be an accurate reflection of the true cost. The slightly longer travel time was the only negative economic impact identified.
“It is estimated that the casualty prevention savings, including the reduced impact on NHS and emergency services, could be up to £92 million every year.”
Ms Mordaunt is the MP for Portsmouth North.
Portsmouth was the “first British city to implement a 20mph speed limit on almost all residential roads to reduce road casualties and protect pedestrians and cyclists”, according to the city council’s website.