Fekir, who nearly completed a move to Liverpool a year ago, has signed on with Betis on a four-year deal, making the move for a reported fee of around €20 million (£18m/$22m).
Another €10m is rumoured to be possible in incentives, with Lyon receiving a 20 per cent sell-on clause.
Fekir’s younger brother, Yassin, also has joined Betis with Lyon said to be receiving a 50% sell-on clause.
The 26-year-old playmaker had spent the entirety of his senior career with Lyon, breaking into the first-team squad in 2013.
The 2014-15 season saw Fekir have his first strong year, scoring 13 goals and adding nine assists, but it was in the 2017-18 campaign where he burst onto the scene.
Fekir scored 18 goals and added eight assists for Lyon, while chipping in another three goals and an assist in the Europa League that season.
His strong campaign earned him a place at the 2018 World Cup for France, as he made six substitute appearances for Les Bleus as they went on to win their second-ever title.
However, Fekir was allegedly on the verge of a big money move to Liverpool, with the Anfield outfit rumoured to be ready to pay around €60m for the playmaker and the player’s former agent, Jean-Pierre Bernes, claiming he even posed for photos in a Liverpool shirt.
But the deal failed to materialise, with reports suggesting the Premier League club took issue with Fekir’s medical. Further reports claimed he also had the interest of clubs such as Real Madrid and Chelsea.
But the player remained with Lyon last season, scoring nine goals and adding seven assists, as well as a further three goals and two assists in the Champions League.
With Fekir only having a single season remaining on his contract and refusing to sign a new deal, Lyon were forced to cash in on the playmaker rather than lose him for free next summer.
Betis will open their 2019-20 season at home against Valladolid on August 19.