The film, which stars Chris Evans as a scrawny World War Two reject given super powers from an experimental serum, easily exceeded the April take for the racing movie "Fast Five," which collected $86.2 million in ticket sales in April 2011.
"Noah," starring Russell Crowe as the biblical figure, was second with $17 million in ticket sales from Friday to Sunday, and has collected $72.3 million in overall domestic sales since opening last week, according to studio estimates.
The dystopian action film "Divergent" was third with $13 million, for a total of $114 million since its March 21 release in U.S. and Canadian theaters.
"Captain America: The Winter Soldier" also scored the biggest opening weekend of 2014, and took in another $9.6 million at IMAX screenings, which charge a premium. That also set a new April record.
"We're off to a great start. This was a great jumping off place for what we expect to be a fantastic run," said Dave Hollis, Walt Disney Studios' executive vice president of film distribution, citing the $177 million film's opening.
"I would certainly expect we can broaden out" beyond the usual Marvel film buyers, said Hollis, noting that some 90 percent of critics had given positive notices as collated by the Rotten Tomatoes website and audiences rated the film an A.
Approaching school holidays should boost ticket sales further, he added.
"Captain America: The Winter Soldier" is the most recent in a growing number of films that Marvel, a unit of Disney, has made from its library of comic book heroes.
Its star, Evans, was among the actors playing their superhero roles in the 2012 film "Marvel's The Avengers," which ranks as the third highest grossing film in Hollywood history with $623.4 million in domestic sales and $1.5 billion worldwide, according to the movie site Box Office Mojo.
Hollis said the latest installment was "tapping into that extraordinary momentum."
Scarlett Johansson, playing the Marvel character Black Widow, also appeared in "The Avengers" and reprises her role in "Captain America: The Winter Soldier."
After only 10 days in release, the new film had surpassed the total international box office of the original installment, "Captain America: The First Avenger," according to Disney.
The film was well on its way to a record weekend by Thursday night, when it collected $10.2 million in late-night showings. It opened a week early in several international markets, where it has already surpassed $207 million, for a global total of $303 million.
Fourth for the weekend with sales of $7.7 million was the independently-released Christian drama "God's Not Dead," which continued its impressive run despite being panned by critics.
Only two of 10 reviewers liked the film, according to Rotten Tomatoes, although 86 percent of those who saw it told the site they liked it.
"The Grand Budapest Hotel" rounded out the top five, taking in $6.3 million. Starring Ralph Fiennes as a scheming concierge and directed by Wes Anderson, the film started slowly, playing in only four theaters on March 7 and has grown steadily. It is currently playing in 1,263 theaters.
Walt Disney Co distributed "Captain America: The Winter Soldier." "Noah" was released by Paramount Pictures, a unit of Viacom.
Lionsgate distributed "Divergent." "The Grand Budapest Hotel" was released by Fox Searchlight, a unit of Twenty-First Century Fox. "God's Not Dead" was distributed by Freestyle Releasing.