The solar-powered, six-wheel rover arrived at Endeavour crater after driving 13 miles from a smaller crater named Victoria.
The drive, which took nearly three years, culminated Tuesday, when Opportunity signaled it had arrived at the location dubbed Spirit Point in honor of the rover's twin, which fell silent last year.
"We're there," said project manager John Callas of NASA's Jet Propulsion Laboratory.
Opportunity and Spirit landed on opposite sides of Mars in 2004 and used their instruments to discover geologic evidence that the cold and dusty planet was once wet.
Craters can provide windows into the planet's past because layers of material from long-ago eras are exposed. Endeavour crater is more than 25 times wider than Victoria.
Callas said the plan is to drive a bit closer to the rim to take pictures of the oldest rocks seen by Opportunity.
"This is a brand new mission," Callas said.
Since landing, Opportunity has studied sulfate sediments that pointed to an environment that was once wetter and warmer.
"Now we have rocks that predate that," Callas said.
The rover's work is part of NASA's Mars Exploration Program strategy known as "follow the water," which looks for evidence that liquid water once existed or perhaps still exists on the planet. Liquid water is considered essential for the potential for some form of life to have developed.
Last week, research based on observations by NASA's Mars Reconnaissance Orbiter theorized that dark, fingerlike features that appear spring through summer on some Martian slopes then fade in winter could be flows of briny water. Saltiness would be necessary to lower the freezing temperature of water.
A big, new NASA rover named Curiosity is awaiting launch from Cape Canaveral, Fla., on a $2.5 billion mission to explore a towering mountain inside a 96-mile-wide crater to determine if there were once conditions capable of supporting microbial life.
Curiosity, powered by a radioisotope instead of sunlight, is expected to land on Mars in August 2012.