The Real Madrid star was making his 110th international appearance and broke the deadlock 21 minutes in with his 48th goal for his country, overtaking Pauleta as Portugal's most-prolific player almost 10 years after scoring his first against Greece in Euro 2004.
Cameroon were in no mood to let sentiment get in the way, however, and equalised two minutes before the break as Vincent Aboubakar hit an emphatic finish under the helpless Beto.
Portugal should have retaken the lead on multiple occasions leading up to the hour mark, but found half-time substitute Guy N'Dy Assembe in good form between the post.
N'Dy Assembe, though, was powerless to prevent Portugal running riot in the last 25 minutes. Raul Meireles capitalised on a glaring defensive error before Fabio Coentrao, Edinho and Ronaldo wrapped up an easy win against a side who will join Portugal at the FIFA World Cup later this year.
Cameroon's first chance of the match arrived in the 11th minute as Aboubakar burst in front of Rolando to meet a corner delivery, but Beto did well to keep the headed effort out to his left.
Joao Pereira cut a precise pass back to Ronaldo on the edge of the area and, after a clever first touch to escape Nicolas N'Koulou, the Ballon d'Or winner drove his historic effort into the bottom-left corner.
Itandje's half-time replacement – N'Dy Aseembe – was forced into action twice in quick succession in the 56th minute as he first palmed away Coentrao's half-volley before tipping a Ronaldo volley around the post.
The Real Madrid man latched on to Cavaleiro's clever disguised pass in the left side of the area before dispatching with admirable composure.
Four became five in the 83rd minute as the Cameroon defence failed to get Miguel Veloso's cutback under control and Ronaldo stole possession away before rifling a low shot past the goalkeeper.
