Ryanair boss Michael O'Leary said the Glasgow Prestwick to London Stansted route would end in three months after APD had made the budget fare unsustainable.
Chancellor George Osborne froze APD in March, but plans a substantial rise next April.
Mr O'Leary said APD had been a "bugbear" of Ryanair, particularly on domestic flights. He said they were pulling the Stansted route at the end of October as it was "nuts" that a £12 APD was imposed on a £9 flight.
Mr O'Leary said: "I would like to see it scrapped. For a flight of £9 you are looking at a duty charge of £12 and £24 for a return - it's nuts and is just not sustainable."
Passengers now pay up to £170 in APD and Glasgow Airport bosses fear numbers could drop by more than 300,000 over the next three years due to rises in APD .
Glasgow Airport has asked for APD to be devolved to the Scottish Government as part of the Scotland Bill on the basis of its progressive approach to aviation.
Amanda MacMillan, managing director of Glasgow Airport, said: "If the aviation industry is to continue to generate employment, encourage export-led growth, support tourism and attract investment, it cannot be subjected to any further increases in APD.
"Our ability to attract new routes will be seriously hampered as airlines will look elsewhere."
Scott Taylor, chief executive of the Glasgow City Marketing Bureau, said: "APD in Scotland and the UK is at disproportionate levels and as a result disadvantages airlines from travelling to other airports within the UK.
"Very often the cost is more than the flight. I think it is unlikely to be scrapped, but will have to have parity with other European countries. It should be devolved to the Scottish Government and a review carried out."
Stuart Patrick, Glasgow Chamber of Commerce chief executive, said APD was an "unhelpful" tax when trying to attract more airlines.
He said: "It has been especially negative for long-haul destinations.
"Good and competitive air connectivity is vital to grow our economy, and APD puts business growth at risk in an already challenging environment."
Glasgow Airport said they had held exploratory discussions with Ryanair, but did not receive any serious note of interest from the airline to build a base at Glasgow Airport.
A spokeswoman said: "The management at Glasgow Airport is focused on running a commercially successful business and ensuring the long-term future of what is one of the most important parts of Scotland's transport infrastructure.
"We're committed to expanding our route network and will work with any airline that is serious about assisting us in doing just that."