Reservations are now open for sailings through Vietnam and Cambodia to explore the river onboard the 124-passenger AmaDara.
Jamie Loizou, managing director of AmaWaterways, said holidaymakers are looking for "authentic experiences in exotic destinations" as confidence returns.
"We are delighted to be returning to the Mekong, which has been an incredibly popular destination for us in the past," he added. "We are seeing strong forward bookings for 2023 and 2024 and, with entry regulations easing, it isn’t too late to travel to this spectacular part of the world in 2022".