Commander Eileen Collins and pilot James Kelly fired up the steering jets at 4.06am Pacific time (1106 GMT) on Tuesday, and they will burn for two minutes and 42 seconds to get Discovery out of orbit and into an unpowered glide towards its home planet.
"Discovery is on its way back to Earth," Mission Control said from Houston, Texas.
The firing of the three rockets had slowed the velocity of the craft by only 300km from its speed of about 27,200 kph for re-entry, Mission Control said.
The orbiter and its crew of seven started their home-bound plunge just over one hour before the scheduled 5.12am (1212 GMT) landing at Edwards Air Force Base in California's Mojave desert.
Landing venue shift
Discovery was initially scheduled to land at Cape Canaveral in Florida, but Nasa shifted the landing spot because of thunderstorms and rain over the Kennedy Space Centre.
The landing site shift will cost Nasa about $1 million.
The 14-day mission was the first since Columbia burst into flames upon re-entry into the atmosphere on 1 February 2003.
Nasa hailed Discovery's mission as a full success, but has decided to ground the shuttle fleet because insulating foam fell off the shuttle's external tank on take-off, the same problem that doomed the Columbia flight.