The Qatar Airways charter flight took off with 305 people on board, said Deo Chandra Lal Karna, an official at Kathmandu's Tribhuvan International Airport.
Immigration official Sagar Acharya said most of the passengers were German nationals or had some connection to the country.
Nepal, home to the highest mountains and hiking trails, is popular with tourists during the spring season when the weather is favorable for climbing.
Up to 10,000 tourists are believed to be stranded in Nepal since the government ordered a complete lockdown that halted all flights and road travel to prevent the spread of the virus. Businesses and government offices were also shut.
Nepal has only three confirmed cases of the coronavirus, including one who has recovered.