Sergio Ramos and Daniel Carvajal also scored for Real who are now second on 82 points, three behind Atletico before they visit Valencia on Sunday with both teams having played 34 games.
Barcelona, mourning the death of former coach Tito Vilanova on Friday, have 81 points and visit Villarreal on Sunday.
Real did not risk Gareth Bale or Karim Benzema against Osasuna ahead of their Champions league semi-final second leg at Bayern Munich on Tuesday in which they hold a 1-0 advantage.
But there was no holding Ronaldo, who only returned from injury in Wednesday's first leg against Bayern at the Bernabeu having been out since early April, as he cut in from the left wing and fired into the corner of the net after six minutes.
The prolific Portuguese forward then cracked home a fine long-range drive after 52 minutes before being substituted leaving Ramos and Carvajal to wrap up the win with headers.
Earlier, Getafe beat Malaga 1-0 to boost their survival hopes and confirm the relegation of Real Betis who host Real Sociedad later on Saturday.