On 15 January 2015, the initial A350-900 entered service with Qatar Airways, followed by the A350-1000 on 24 February 2018 with the same launch customer. As of October 2023, Singapore Airlines is the largest operator with 63 A350-900 aircraft in its fleet.

In 2026, the Airbus A350 has become the backbone of many major long-haul fleets due to its fuel efficiency and quiet cabin. The world's largest operator of the A350 is Singapore Airlines, which uses the aircraft for its ultra-long-haul routes, including the record-breaking flight from Singapore to New York. Other massive operators include Qatar Airways (the launch customer for the -1000 variant), Cathay Pacific, Air France, and Lufthansa, which is steadily replacing its older A340s with new A350s. In the United States, Delta Air Lines is the only major carrier to operate the type, having committed to the A350 as its primary flagship for transpacific and transatlantic missions. Other notable airlines using the A350 in 2026 include Turkish Airlines, British Airways, Iberia, and Thai Airways. This aircraft is highly favored by passengers for its "Airspace" cabin, which features larger windows, higher humidity levels, and lower cabin altitude, significantly reducing the effects of jet lag on flights exceeding 10 hours.