The Portuguese forward, sidelined since February, had missed Al Nassr’s previous two league matches and was also ruled out of Portugal’s friendlies against Mexico and the United States last month.
Al Najma, who have won only once in 27 league games, took a surprise lead a minute before halftime through Rakan Al Tulayhi.
Al Nassr responded swiftly, with Abdullah Al Hamdan and Sadio Mane scoring in first-half stoppage time to turn the match around.
The visitors drew level two minutes after the restart when Felippe Cardoso struck, but Al Nassr regained control when Ronaldo converted a penalty in the 56th minute.
The 41-year-old added his second in the 73rd minute before Mane sealed the win with a stoppage-time strike.
Al Nassr’s 13th consecutive league victory kept them top of the standings on 70 points, six clear of second-placed Al Hilal, who play Al Taawoun on Saturday.