The 27-year-old, who has been capped 12 times, has signed a five-and-a-half-year contract, after spending the first 10 years of his senior career with Les Dogues.
Debuchy will re-join his close friend Yohan Cabaye at St James' Park, with the duo having helped Lille to a league and cup double in 2011.
The Magpies are believed to have paid in the region of £5m for Debuchy, who will wear the number 26 shirt but will not be in the squad for Saturday's FA Cup tie at Brighton.
"It is great to become a Newcastle United player," said Debuchy. "After many great years at Lille I felt I was ready for a new challenge and cannot wait to play for such a big club, in the best league in the world.
"I hope I can bring something fresh to the team and help us get up to the highest possible placing in the Premier League this season. I will give everything for this club."
Newcastle boss Alan Pardew added: "We are absolutely delighted to have finally secured the signature of Mathieu.
"It's no secret we've been trailing him for a while now and to have reached this point fills me with great excitement and anticipation in respect of what he will be able to offer the team.
"At the same time it's a huge relief to actually have him with us now. He is an established top international player and it is a huge coup for this club that we now have him at St James' Park.
"Mathieu will add real quality to our team, in terms of his ability, character and experience, and I am sure he will quickly become a firm favourite among our fans too."
Debuchy caught the eye for France at Euro 2012, particularly impressing in their opening game of the tournament, a 1-1 draw with England.