A dust storm that swept the planet in May 2018 is suspected to have blocked the machine from receiving sun rays to charge its solar panels.
Engineers in the Space Flight Operations Facility at NASA's Jet Propulsion Laboratory (JPL) made their last attempt to revive the rover on Tuesday but to no avail.
Deputy project scientist Abigail Fraeman was a 16-year-old high school student when Opportunity landed on Mars; she was inside the control center as part of an outreach program.
Opportunity landed on Mars in 2004 and covered 28 miles (45 km) on the planet.
Project manager John Callas said: "It's just like a loved one who's gone missing, and you keep holding out hope that they will show up and that they're healthy".
Opportunity was the fifth of eight spacecraft to successfully land on Mars so far, all belonging to NASA.
"But each passing day that diminishes, and at some point you have to say "enough" and move on with your life".
Mars One, which offered 1-way trips to Mars, declared bankrupt
Later that year, we reported that the Mars One mission was essentially uninsurable . The news was confirmed by the company's founder, Bas Lansdorp, to Engadget .
It had already lost its identical twin, Spirit, which was pronounced dead in 2011, a year after it got stuck in sand and communication ceased.
Callas believes it is "good luck that we skirted so many possible storms" over the years.
The experience inspired her to pursue a career at JPL; Fraeman is now a deputy project scientist on the Mars exploration rover project, and works with Opportunity nearly daily.
Its greatest achievement was discovering, along with Spirit, evidence that ancient Mars had water flowing on its surface and might have been capable of sustaining microbial life.
Cornell University's Steve Squyres, lead scientist for both Opportunity and Spirit, considers succumbing to a ferocious storm an "honorable way" for the mission to end.
The swirling maelstrom may have dumped dust onto the solar panels which power the rover, meaning it can not recharge its battery to make contact with mission control back on Earth.
Nasa wrote: 'The solar-powered rover last communicated with Earth on June 10, 2018, as a planet-wide dust storm was blanketing the Red Planet'.
When the sky finally cleared, the rover remained silent, its internal clock possibly so scrambled that it no longer knew when to sleep or wake up to receive commands. "Mars is now part of our neighborhood".