The 31-year-old has moved for $500,000 after agreeing personal terms with the Galaxy.
De Jong's contract is set to run until 2018, with the midfielder assuming a designated-player spot after Steven Gerrard's departure at the end of the season.
"I knew that it was going to be a complicated deal because I had just renewed my contract with AC Milan, but I was interested from the start," De Jong told the club's official website.
"I thought that it would be the perfect time for me to go to the States because of my age. Instead of being a little bit older, I'll be heading over in the best part of my career. That's when I decided that I wanted to go to the Galaxy."
The Dutchman played a total of 96 games for AC Milan after joining from Manchester City for $3.8 million in 2012.
Galaxy's head coach Bruce Arena lauded De Jong's ability to play at the center of the park.
"I think Nigel brings us a very experienced player in the center of midfield. He's a player whose qualities will help the players around him."
"He's an outstanding defensive midfielder. He has great mobility and can obviously win tackles and distribute the ball quickly. He's really going to complement the players ahead of him."
The move sees De Jong join Dan Kennedy, Jeff Larentowicz, Mike Magee, Emmanuel Boateng, Jelle Van Damme, and Ashley Cole in Galaxy's long recruitment list for the 2016 MLS season.