The Premier League champions received an unconditional offer of £80 million pounds ($NZ205m) for Ronaldo, and unlike in the last offseason is willing to see its 24-year-old star performer join a major European rival.
United said: "At Cristiano's request - who has again expressed his desire to leave - and after discussion with the player's representatives, United have agreed to give Real Madrid permission to talk to the player.
"Matters are expected to be concluded by 30 June."
The Portugal winger spent last June pushing for what he called at the time a "dream move" to Madrid, but any transfer was blocked by United manager Alex Ferguson, who traveled to Lisbon to persuade his player to stay at Old Trafford.
That didn't stop Ronaldo being linked with Madrid and Ferguson's irritation boiled over in December when he said he "wouldn't sell Madrid a virus," describing the club as a "mob."
But now a world-record bid appears too hard to resist for the heavily indebted Premier League club.
Ronaldo, who was under contract until 2012 at United, plunged his future into doubt after losing the Champions League final to Barcelona last month, despite having vowed to stay at United in the buildup to the match and even in a broadcast interview conducted with himself.
The return of Florentino Perez as Madrid's president has changed things as he looks to spend to return the Spanish side to the glory days of its "galactico" era.
Kaka was signed from AC Milan earlier this week for a reported fee of around €65 million ($NZ142 million).
But the offer for Ronaldo would eclipse that and the $65 million it paid to get former France striker Zinedine Zidane from Juventus in 2001.
