The Portuguese star, who has had to soak up a lot of criticism for a lacklustre tournament by his high standards, powered in a 50th-minute header to put his side in front.
Ronaldo then had his mis-shot turned in by Nani for a second goal three minutes later, ending Wales' remarkable run at their first major finals since 1958.
The Portuguese, who had not won a single game in the tournament over 90 minutes, next meet hosts France or Germany, who play their semi-final tomorrow.