The Spain-born Dominican Republic international came through Real’s academy, making eight substitute appearances for the first team and scoring once before departing for Lyon in 2017.
The 25-year-old started 30 Ligue 1 games last season, netting 18 goals as his side finished third and secured Champions League qualification.
Mariano was strongly linked by Spanish media with a move to Sevilla before the transfer window closes at the end of this month, but European champions Real exercised their right to trigger the buy-back option in the deal when he left the club.
He represents the only major attacking arrival at the Bernabeu since Cristiano Ronaldo's departure last month.
Real have not commented on the figures involved, but a Lyon club statement said the deal was worth about 33 million euros (29.69 million pounds).
(Reporting by Joseph Cassinelli, editing by Ed Osmond)
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