The daily, non-stop journey from Changi to Newark Airport will cover about 16,700 kilometres (10,300 miles) and take about 18 hours 45 minutes, the airline said in a statement.
The current record holder is Qatar Airways Flight 921 from Auckland to Doha, which takes 17 hours 40 minutes.
The Singapore Airlines flight will use the long-range Airbus A350-900ULR, which will be configured to carry 161 passengers -- 67 in business class and 94 in premium economy.
The airline had flown a similar route from 2004 until 2013 but cancelled it as it fell short of revenue expectations. However, its latest decision comes as carriers look for new sources of revenue in a competitive environment, while long-haul flights often make more cash than those that require stops.
There are also plans for a non-stop route from Singapore to Los Angeles using the same plane, the airline said.
The new route comes as the city-state's flag carrier faces tough challenges.
Last year, it consolidated its low-cost units TigerAir and Scoot into a single entity in a streamlining exercise.
And this month it said it will absorb its struggling premium regional wing, SilkAir, into the broader group following a multi-million-dollar upgrade as part of reforms to stay competitive.