Erik ten Hag’s side have been looking to reinforce their midfield all summer and a deal worth an initial 60million euros (£50.7m) is close for the Brazil international.
The fee for Casemiro could rise to 70m euros (£59.2m) if clauses are met, with a four-year deal plus the option of a further season on the table.
Talk of a medical on Friday appears premature, which means he would not be registered in time for Monday’s clash with rivals Liverpool.
United sit bottom of the Premier League after their 2-1 home defeat to Brighton was compounded by last weekend’s 4-0 humbling at Brentford.
Casemiro – a former team-mate of Cristiano Ronaldo and Raphael Varane in Spain – is a five-time Champions League winner with Madrid, who he joined from Sao Paulo in his homeland in 2013.
More irons are in the fire as United look to kickstart their ailing campaign at a time of intense pressure on the Glazer family.
Protests are planned against the owners before and during Monday’s clash with Liverpool and Sir Jim Ratcliffe has publicly declared his interest in buying the club.