The Cygnus cargo ship is the seventh of 10 planned missions through 2018 under Orbital's space station resupply contract with NASA, worth up to $3.1 billion.
The Atlas V launch was delayed from March 24 after a hydraulic issue was discovered on ground support equipment.
"We are carrying more this time than we have in the past and that's a good step forward for us and for the crew", Frank Culbertson, president of Orbital ATK's Space Systems Group, told reporters during a pre-launch news conference.
Orbital ATK previously bought two Atlas V rides to the space station to fill a gap while Antares was retrofitted with new engines.
While missions to be launched Russian Federation and the United States represent business as usual, China is aiming to take another major step along the trail blazed by the two pioneers of the early space age. Orbital is trying to increase the amount of payload that the Cygnus can carry on both the Atlas and the Antares, and the company plans to launch its next mission on the Antares as early as this summer.
It's launch day for a United Launch Alliance mission named after John Glenn, an astronaut and former US senator who once rode into space on a predecessor of the rocket that launches today.
NASA also hired privately owned SpaceX to fly cargo to the station.
Normally it takes two to three days for cargo vehicles to meet up with the ISS, but the Cygnus is actually going to hang out in orbit for a little while once it launches. The launch scheduled for Thursday will deliver the new crew to the station in about six hours after liftoff.
One experiment on board is a sophisticated new greenhouse that will be evaluated as a way to grow food for astronauts during long-duration stays in space.
The Cygnus is also carrying 38 small satellites known as CubeSats, many of which have been built by college students. At that point, Orbital will light a large fire inside the vehicle again - the third time this has been done in a departing Cygnus to study how flames behave in microgravity.
ULA's 71st Atlas V rocket is scheduled for launch at 11:11 a.m. EDT (1411 GMT) from Cape Canaveral Air Force Station in Florida. Weather conditions were ideal for the launch, and NASA broadcast the event on its NASA TV media channel.
Tuesday's launch marked the first time NASA, in coordination with the ULA and Orbital ATK, has broadcast a rocket launch with a 360-degree view, which should "virtually place the public at the base of the rocket during launch".