Distributor Walt Disney said the film earned $US205 million ($A313 million) in US and Canadian ticket sales.
The returns set a record for an R-rated film and topped the $US154.2 million ($A235.2 million) collected by another Disney film, the animated Pixar movie Inside Out 2, when it debuted in June.
Deadpool & Wolverine, the first R-rated Marvel film by Disney, stars Ryan Reynolds as Deadpool, a character known for sexually explicit jokes, swearing and violence. Australian Hugh Jackman plays Wolverine, a sharp-clawed mutant.
The movie opened in international markets on Wednesday and has brought in $US233.3 million ($A355.8 million) outside of the US and Canada, Disney said.
With AAP.