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A black and white photo of the publication's Manhattan headquarters takes pride of place, with the strapline #lastprintissue.
The nod to Twitter is regarded as a backhanded compliment.
The death of the print edition was caused by falling advertising revenues, as audiences moved online.
From the new year, Newsweek will be a digital-only publication. Editor Tina Brown described it as "a new chapter" for the magazine.
In a defiant editor's letter, she wrote: "This is not a conventional magazine, or a hidebound place.
"It is in that spirit that we're making our latest, momentous change, embracing a digital medium that all our competitors will one day need to embrace with the same fervor.
"We are ahead of the curve."
Ms Brown became editor of the publication two years ago, after it merged with The Daily Beast, a news website she co-founded in 2008.
Newsweek's first edition was published on 17 February, 1933. It made an immediate splash with its front cover, featuring seven photos - one news story for each day of the week.
Although it always took second place to its rival, Time, it  gained prominence in the 1960s for its coverage of the civil rights movement.
At its height, it had a circulation of 3 million, but declining readership and advertising revenue saw it fall into losses.
It was sold by the Washington Post Company to businessman and publisher Sidney Harman for $1 in 2010, and was merged with the Daily Beast three months later.
Ms Brown is a former editor of Vanity Fair and The New Yorker. She unveiled Newsweek's final front cover via Twitter, saying: "Bitter sweet! Wish us luck!"
One reader commented that the hashtag headline was "like using your final breath to ID the killer".
The move to a digital edition will allow Newsweek to cut costs such as printing, postage and distribution. However it will lose money from print advertisers, who traditionally pay more than their online counterparts.
As the final edition went to the printers, The Daily Beast confirmed it would be making many of its editorial staff redundant.

The 777-200, which was carrying 294 passengers from Paris to Vancouver, was diverted to Prestwick after taking off at 10:57 on Saturday.
The airline said the plane landed "normally" at 13:20 local time.
Air France added that it had sent a second aircraft to Prestwick in order to fly the passengers back to Charles de Gaulle Airport on Saturday.
In a statement, it said: "Air France confirms that flight AF374 operating from Paris CDG to Vancouver on 15 July, 2017, was diverted to Glasgow Prestwick where it landed normally.
"Following the appearance of a slight smell of burning on board, the cabin crew, trained for this kind of situation, took the necessary precaution and diverted to the closest airport."
The 80-year-old US current affairs magazine Newsweek has revealed the image that will grace the cover of its last-ever print edition.
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An Air France passenger jet has made an emergency landing at Prestwick Airport after fumes were detected on board.