The movie, which stars Chris Evans, Robert Downey Jr and Scarlett Johansson is expected to eclipse 2014`s Captain America: The Winter Soldier at $259m (£179.2m) by the end of next weekend.
It includes a much-publicised fight between Captain America and Iron Man.
Plus there are introductions of new characters in Chadwick Boseman`s Black Panther and Tom Holland`s Spider-Man.
Its opening record trails Star Wars: The Force Awakens, which opened at $248m (£172m), Jurassic World at $208.8m (£145m), Marvel`s The Avengers at $207.4m (£144m) and Avengers: Age of Ultron at $191.3m (£132.4m) .
2011`s Captain America: The First Avenger opened at $176.6m (£122.2m).
Captain America is also keeping the US box office on track for a record performance in 2016 with $3.856bn (£2.669bn) through this weekend.
Disney has played a major role in that gain with The Jungle Book and Zootopia delivering blockbuster numbers.
Star Wars: The Force Awakens provided $285m (£197m), or 30% of its $936m (£648m) total.
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