The budget airline's chiefs said they had no plans to pull out of the taxpayer-owned Ayrshire hub as the Scottish Government came under pressure to publish a business plan for its investment.
Liberal Democrat MSP Jim Hume said: "Less than nine months after stating that they were committed to Prestwick, Ryanair's decision to remove [nearly half] of its routes away from the airport is upsetting news for all involved. At a time when we need to work together to ensure the viability of the airport that is an important contributor to the Ayrshire economy, I am disappointed that Ryanair hasn't backed up its words with actions."
Alex Johnstone, Scottish Conservative transport spokesman, said the development was a disaster for the Scottish Government and demanded "urgent details" on how it intends to return the airport to profitability.
Ryanair will cut its winter routes from Prestwick from 13 to seven from October, retaining sunshine destinations while services to Dublin, Derry, Riga, and Poland to Glasgow. It is the first time the budget carrier has had a base in the city.
The new winter schedule will also include new direct flights three times a day from both Glasgow and Edinburgh to London Stansted.
Kate Sherry, deputy director of route development for Ryanair, said: "I don't want what we're announcing today to be read as Ryanair pulling out of Prestwick. Our commitment to Prestwick remains. We have had some talks with the Scottish Government in relation to future developments and we are currently working on our summer schedule for 2015.
"As well as our passenger operation we have 300 engineering staff at the hangar and maintenance base in Prestwick, so yes, it is our intention to stay there. This is good news for Scotland, with the creation of 500 new jobs overall."
Ms Sherry added that Ryanair backed the Scottish Government's ambition to reduce and eventually scrap air passenger duty (APD), which is currently reserved to Westminster. "Scotland cannot unlock its full potential until APD is repealed," she said.
Ryanair bosses said they expected to carry about 500,000 passengers a year from Prestwick, which last year recorded passenger traffic of 1.1 million.
The announcement comes weeks after Nicola Sturgeon announced £10 million in funding to cover operating costs, the clearing of a maintenance backlog and an overhaul of the duty-free lounge. The Scottish Government has already spent about £5.5m since buying the airport for £1 last year.
A "strategic vision document", based on the recommendations of finance consultant Romain Py, is expected to be published by the Scottish Government in August. The full report, which cost taxpayers £100,000, has been withheld to avoid disclosing commercially confidential material that it was feared could harm Prestwick's recovery.
Bill McIntosh, leader of South Ayrshire Council, said he was disappointed by the development but believed there was still an "essential role" for Prestwick.
A spokesman for the Scottish Government said: "Whilst the number of routes from Glasgow Prestwick Airport is fewer than offered last winter, Ryanair has assured us of its continuing commitment to the airport and of its intention to actively consider growth options in the future.
"These service changes are part of the normal revision process that airlines undertake to optimise their business."