The 22-year-old arrives in west London after spending just one season at Molineux, having previously played for Stoke and Burnley, and has 45 Premier League appearances to his name.
Bees head coach Thomas Frank likes what he has seen from Collins and feels he will prove to be “a perfect Brentford player”.
“I’m very pleased that we’ve managed to sign Nathan,” Frank told the club’s website.
“He’s a very talented centre-back and still young. He has a lot of very good abilities that we value a lot. He’s a composed and calm defender.
“His heading in both boxes is a big thing, both in open play and from set-pieces, which is massive in the Premier League.
“His character is really good, and we know that character is everything. He will fit into our culture, I have no doubt about that.
“I see leadership potential in Nathan. He’s a perfect Brentford player – hungry and ambitious with a desire to learn.”
Collins, who cost Brentford a reported £23million, is now aiming to help the club build on their highest-ever league finish after they ended the 2022-23 term in ninth place.
“I talked with the manager and a few of the backroom staff about the project here,” he said.
“It’s a club on the rise and I can see where they want to go. It’s exciting to be here.
“I like to play football. I want to dribble, play and create. It starts at the back. I can play long balls and short balls. But, at the end of the day, I’m a defender and I have to head the ball, win it and win my challenges.”
The arrival of Collins comes on the back of Brentford signing goalkeeper Mark Flekken from Freiburg, with Kevin Schade’s loan from the Bundesliga side also made permanent this summer.