Ground controllers at the space agency's lab in Pasadena, California, celebrated wildly after receiving confirmation the rover touched down on the red planet.
Thomas Zurbuchen, NASA’s science mission chief, said “now the amazing science starts,” with the probe set to collect rocks to eventually bring back to Earth for scientific examination.
Deputy project scientist, Ken Williford, said: "Are we alone in this sort of vast cosmic desert, just flying through space, or is life much more common? Does it just emerge whenever and wherever the conditions are ripe?”
“We’re really on the verge of being able to potentially answer these enormous questions.”
The six-wheeled rover, nicknamed Percy, landed on an ancient river delta and lake known as Jezero Crater, which has a diameter of around 30 miles.
The crater is a five by four mile strip on an ancient river delta full of pits, cliffs and rocks.
Scientists believe if life ever flourished on Mars, it would have happened 3 billion to 4 billion years ago, when water still flowed on the planet.
Percy will drill down into the planet using its seven-foot arms and collect rock samples containing possible signs of bygone microscopic life.
Three to four dozen chalk-size samples will be sealed in tubes and set aside to be retrieved eventually by another rover and brought homeward by another rocket ship.
The goal is to get them back to Earth by as early as 2031.
Nasa has teamed up with the European Space Agency to bring the rocks home. Perseverance’s mission alone costs nearly $3 billion.
The only way to confirm - or rule out - signs of past life is to analyze the samples in the world’s best labs. Instruments small enough to be sent to Mars wouldn’t have the necessary precision.
“It’s really the most extraordinary, mind-boggingly complicated and will-be history-making exploration campaign,” said David Parker, the European agency’s director of human and robotic exploration.
Former astronaut and one-time NASA science chief John Grunsfeld tweeted that Perseverance’s landing was “exactly the good news and inspiration we need right now.”
“Reminds us all that we will persevere Covid and political turmoil and that the best is yet to come,” he said.
What will the rover do?
It is Nasa’s most ambitious Mars mission yet, totalling around £2.16 billion ($3 billion).
Besides seeking signs of past microscopic Martian life, Perseverance will also release a spindly, 4lb (1.8kg) helicopter that will be the first rotorcraft ever to fly on another planet.
Its cameras will shoot colour video of the rover’s descent, providing humanity’s first look at a parachute billowing open above Mars, while microphones capture the sounds.
The rover will also attempt to produce oxygen from the carbon dioxide in the thin Martian atmosphere.
This is important because extracted oxygen could someday be used by astronauts on Mars to breathe as well as for making rocket propellant.
While prowling the surface, Perseverance will peek below, using radar to locate any underground pools of water that might exist.