Ronaldo, the world’s most expensive player, paraded the Golden Boot before kickoff for the 40 league goals he scored last season, and he helped his bid to win it again with a hat-trick at the Bernabeu.
Argentina winger Di Maria set up the first three goals for Ronaldo, Pepe and Gonzalo Higuain before being carried off with what looked like a thigh injury at the start of the second half.
Ronaldo notched up his second goal from the penalty spot in the 54th when Osasuna had defender Eneko Satrustegui sent off, and he bagged his fourth league treble this season in the 57th, taking his La Liga tally to 13.
Substitute Karim Benzema wrapped up the scoring with two more goals.
Injury-hit Osasuna, who were thrashed 8-0 away to Barcelona in September, had drawn level at 1-1 in the 31st minute when Ibrahima took advantage of a quickly-taken free kick to beat Iker Casillas.
Real climbed to 28 points from 11 games, four clear of second-placed Barcelona, who can close the gap back to one point with a win at Athletic Bilbao later on Sunday (1900 GMT).
Valencia are third with 24 points after winning the city derby 2-0 at Levante on Saturday, pushing the season’s surprise early pace-setters down to fourth with 23 points.