After a lengthy battle, the streaming giant emerged as the highest bidder for Warner Bros., ahead of competitors Comcast and Paramount Skydance.
Warner Bros. owns franchises such as Harry Potter and Game of Thrones, and the streaming service HBO Max.
The takeover would significantly transform the US film and media industry, but analysts have warned it could face opposition from competition authorities.
The cash and stock deal values each Warner Bros. share at $27.75, with a total enterprise value of approximately $82.7 billion.
Netflix co-chief executive Ted Sarandos said that by combining Warner Bros.'s library of shows and films with the streaming platform, "we can give audiences more of what they love and help shape the next century of storytelling."
Netflix's other co-chief executive, Greg Peters, said the deal means Netflix can make Warner Bros. products accessible to more people.
Warner Bros. President and Chief Executive David Zaslav said the announcement "unites two of the world's greatest storytelling companies."
He said, "By joining forces with Netflix, we will ensure that people everywhere can continue to enjoy the world's most compelling stories for generations to come."
Paramount made an initial bid in October to acquire the entire company, including its cable networks like CNN. Warner Bros. declined the move before deciding to sell itself.
There were widespread reports that Netflix was the frontrunner for Warner Bros., but before the announcement, Emma Wall, chief investment strategist at Hargreaves Lansdown, said the US competition regulator was likely to get involved, regardless of the winner.
"This will create a global megapower in broadcast entertainment that regulators will want to pay attention to," she said. Tom Harrington, head of television at Enders Analysis, said it's difficult to predict whether the deal will receive regulatory approval, but if it does, it would have a significant impact on cinema.
He said, "If it goes through, it would mark a new direction for Hollywood, with a streamer buying a business it's essentially the opposite of - Netflix has always had some limited use for cinema, but its offerings generally undermine it."
Mr. Harrington said the merged company would likely lead to a "significant reduction" in television and film production, leading to opposition from some parts of Hollywood and its associated unions.
He said, "HBO, a creative gem, would be severely exposed within Netflix, even though it has survived difficult owners for most of its time."
Mr. Harrington said that for consumers, the merger would likely increase costs.
"Netflix will become more expensive, and even though HBO Max will be shut down/become non-essential, Netflix's greater penetration in homes means overall subscription revenue will increase."