The Portuguese footballer wore the number during his first appearance at the club after inheriting it from David Beckham.
Manchester United confirmed the news on their Twitter account on Thursday night.
The number has previously been worn by George Best, Bryan Robson and Eric Cantona.Between 2003 and 2009, Ronaldo made 292 appearances at the club, scoring 118 goals, winning nine trophies including three Premier League titles and the UEFA Champions League.
Reacting to the news, Ronaldo said: "I wasn't sure if it would be possible to have the number again, so i would like to say a huge thank you to Edi for this incredible gesture."
United's new signing who was allocated no.7, El Matador will switch to no.21, the same number he wears for the Uruguayan national team.
Ronaldo could make his second debut at home to Newcastle United on Saturday 11 September.