Each flight will take less than eight hours with round-trip tickets for a one-week itinerary costing about S$650 (US$503), according to information on the airline's website.
At present, there are no direct flights from Changi Airport to Muscat International Airport or Salalah International Airport, which is Oman's secondary international airport.
The route will be served by a Boeing 737 Max aircraft, which is configured with 12 business class seats and 150 economy class seats, the website showed.
Oman Air chief executive Con Korfiatis said the new route builds on the airline's expanding network while strengthening connectivity between Oman and Singapore, The Straits Times reported.
Oman is known for its traditional architecture and marketplaces, or souks, as well as its diverse landscapes, which range from deserts and mountains to extensive coastlines.
Scuba diving near Muscat is a popular activity.
Currently, about 100 airlines operate some 7,000 weekly scheduled flights from Changi Airport, connecting Singapore to more than 160 cities worldwide.