The film is now the first in Hollywood history to ring up more than $100m in its second weekend of release.
It is the movie's second record, after scoring the biggest-ever US opening weekend, with takings of $207.4m.
The blockbuster sees a team of Marvel comic-book heroes team up to fight an extra-terrestrial threat.
Among the cast are Robert Downey Jr, Scarlett Johansson and Chris Hemsworth - who have appeared in previous Marvel movies as Iron Man, Black Widow and Thor, respectively.
Globally, the film looks set to top the $1bn mark this weekend, distributor Disney said on Sunday.
The Avengers' performance this week left Tim Burton and Johnny Depp's Dark Shadows standing in the dust.
Their spoof horror movie, which opened on Friday, made an otherwise-respectable $28.8m, taking second place at the box office.
Romantic comedy Think Like a Man finished in third place with ticket sales of $6.3 million.
'Super-dope'
The Avengers was directed and co-written by Joss Whedon, creator of the TV series Buffy The Vampire Slayer.
An Oscar-winner for his work on Toy Story, Whedon has had a notoriously rough decade - with TV series Firefly and Dollhouse cancelled, and his horror film Cabin In The Woods delayed by three years due to financial trouble at MGM.
After The Avengers took $207.4m in the US last week - the biggest opening weekend on record - Whedon posted a public letter on his website, thanking his supporters.
"Topping a box office record is super-dope," he wrote.
"People have told me that this matters, that my life is about to change. I am sure that is true. And change is good - change is exciting.
"What doesn't change is that I've had the smartest, most loyal, most passionate, most articulate group of - I'm not even gonna say fans. I'm going with 'peeps' - that any cult oddity such as my bad self could have dreamt of."
Whedon also faced up to the fact that his box office success could soon be eclipsed by The Dark Knight Rises - the heavily-anticipated final chapter of Christopher Nolan's Batman trilogy.
"I will feel sad," he admitted, "but let's look at the bigger picture".
"I can't say this enough: This is not a zero sum game. Our successes, whoever has the mostest, are a boon to each other."
Elsewhere in the US box office, The Hunger Games held on to the number four spot, bringing its total domestic takings to $388m.
Zac Efron's romantic drama The Lucky One was at number five, while two British films took spots in the top ten.
Aardman's Pirates! was at number six, taking $3.1m, while comedy The Best Exotic Marigold Hotel jumped from 16 to eight, taking $2.7m.
