No Way Home scored the third-largest preview total ever, trailing only those for Avengers: Endgame with $60 million and The Force Awakens $57 million.
"Spider-man: No Way Home" took in $50 million at US and Canadian movie theaters, the third-highest total for preview showings ahead of what is expected to be a massive weekend at cinemas that have struggled through the pandemic.
Thursday's sales set a record for the Covid-19 era. Box office analysts predict total domestic receipts for "No Way Home" through the weekend could reach as high as $240 million, which would land it in the top five movie debuts of all time.
The big-budget superhero movie co-produced by Sony Corp and Walt Disney Co stars Tom Holland as the web-slinging superhero and Zendaya as his girlfriend, MJ.
The movie is playing exclusively in theaters.
The film's early success was welcome news for cinema chains, including AMC Entertainment Holdings, Cinemark and Cineworld's Regal chain.
Cinemark said "No Way Home" delivered its biggest opening night sales of all time.
Shares of AMC, a so-called meme stock favorite among retail investors, jumped 23.5 percent to $30.19 in an active trading session on Friday. Shares of Cinemark rose 2.9 percent at $16.63.
Expected weekend revenue: $240 million
The returns show that the film is drawing many moviegoers for the first time during the pandemic, even with the spread of the new Omicron variant, said Shawn Robbins, chief analyst with BoxOfficePro.com.
"This is also an example of having the right content at the right time with the holiday corridor beginning full swing," he said.
Robbins predicted "No Way Home" will finish the weekend between $190 million to $240 million at domestic theaters.
The biggest opening of the pandemic so far was the superhero film "Venom: Let There Be Carnage," which took in $90 million domestically over its first three days in October.
"No Way Home" received a glowing reception from movie critics. As of Friday, 95 percent of 220 reviews were scored as positive on the Rotten Tomatoes website.