The country's key industrial plant faces a walkout from 7am on October 20 after 81.4% voted for a strike and 90% for other forms of industrial action, on an 86% turnout.
The Scottish and Westminster Governments both spoke of "disappointment" at the development and called for renewed negotiations between the Unite union and Ineos, the site's owners.
Motoring experts predicted little impact at filling stations due to the way the UK supply sector has developed, with the AA's Luke Bosdet saying a 48-hour stoppage was unlikely to lead to problems. But Ineos' chairman Calum MacLean said the union "could effectively shut much of Scotland".
The dispute involves two issues - the long-term future of the refinery, amid warnings the site will close by 2017 without investment and reduced costs, and disciplinary action against Stephen Deans, the union official at the heart of the recent vote-rigging row in the local Labour constituency.
The union argues that, with police and Labour party investigations clearing Mr Deans, the firm is being vindictive in pressing on with the action.
A spokesman for the Scottish Government said: "This reinforces our fundamental view that this dispute can only be properly and fully resolved by negotiation between the company and the trade union.
"We will now redouble our efforts to encourage negotiation to avert a strike, while taking forward contingency planning activity."
The union's Scottish Secretary, Pat Rafferty said: "Unite has made every effort to pull Ineos back from the brink but at every opportunity this company has kicked our proposals for peace into touch.
"We have pleaded with Government ministers in Westminster and Holyrood and the joint owners of the Grangemouth refinery Petrochina to help rein in this reckless company before it's too late.A damaging strike may shut down the Grangemouth site, with serious ramifications for fuel production and supply throughout Scotland and the North of England."
Ineos said it had "relatively high" fuel stocks at Grangemouth, adding it would look to bring in additional imports.
But Mr MacLean warned: "The strike could tip Grangemouth over the edge. Ravenscraig, MG Rover and Coryton have all disappeared. Unless we find a way back from the brink, Grangemouth will be next."
Scottish Conservative energy spokesman Murdo Fraser said: "This is a very unfortunate development at a time when there's already a question mark over the future of the plant. It's the last thing it needs."
Energy Secretary Edward Davey said: "I urge the union to call the strike off and for both parties to enter into talks about the long-term future of the plant.
"We have been working closely with the fuel industry and Scottish Government to put robust alternative supply routes in place in the case of a strike, which means that motorists can carry on as normal, and other impacts will be kept to a minimum."