The France-born defender, who had two years left on his contract with the Premier League club, has agreed a deal worth 31 million euros (£26m) which runs until 2028.
Niakhate returns to France where the 28-year-old began his youth career in Lille before moving to Valenciennes in the 2014-2015 season and Ligue 1 side Metz in 2017.
He joined Bundesliga club Mainz for 10 million euros in 2018, playing four seasons before joining Nottingham Forest in 2022 where he played 37 matches.
Niakhate has 11 caps with Senegal since 2023, having played for France's youth teams.
His deal comes 24 hours after Lyon announced they had sealed a deal with manager Pierre Sage until 2026.
Sage, 45, had stepped in as a temporary replacement for Italian Fabio Grosso in November 2023, with the former multiple French champions languishing last in Ligue 1 with a mere seven points.
He revived the club's fortunes with Lyon finishing the season with 46 points in sixth place to qualify for the Europa League, and making it to the French Cup final.
