American Airlines is pulling out of Birmingham Airport.
The airline has operated a daily service to New York since May last year but will stop flights from 6 January.
Birmingham Airport described the decision as “disappointing”, and said it was down to passenger demand.
“Passengers booked on AA flights after 6 January will be contacted by AA to make alternative arrangements or arrange a refund,” the airport spokesman said.
But they added that the airport was “optimistic that another carrier will fill this gap shortly”.
“There remains a strong demand from both the Midlands and North American market wanting to access these important regions and cities.”
The airport said passengers could still travel non-stop to New York Newark with United Airlines, and there continue to be regular connections to North America with several other carriers.
A spokesman for American Airlines said: “As the world’s largest airline, American constantly evaluates our network to ensure we are maximizing our fleet and profitability while matching customer demand.
“Many factors influence network planning decisions; route performance is monitored over time to ensure that American is better positioning itself for long-term success against global competition.”
The airline said it remained committed to serving the UK market and would continue offering flights to the US from four other UK airports.