Ivica Olic sent Croatia on their way with an early opener before Alex Song was shown a straight red card before half-time following a punch on Mario Mandzukic.
Croatia made their numerical advantage count in the second half with Ivan Perisic doubling their lead early in the second half before Mandzukic helped himself to a quick-fire brace to send Cameroon crashing out of the tournament.
The win moves Croatia to three points with Brazil and Mexico on four points as the three battle to qualify for the knockout stages.
Croatia play Mexico next Monday with a place in the knockout stages at stake, while Cameroon are out ahead of their clash with Brazil.
Their frustrations appeared to boil over when Benoit Assou Ekotto and Benjamin Moukandjo had a dispute on the field, with the full-back perhaps fortunate to avoid a sending off for an apparent headbutt on his team-mate.
Cameroon were without talisman Samuel Eto'o due to a knee injury, while Croatia had striker Mandzukic available again following his suspension for his dismissal in the play-off with Iceland last November.
Cameroon were soon behind when they failed to clear Darijo Srna's cross towards Mandzukic.
Perisic had the composure to deliver a finely-weighted diagonal pass across the area for Olic to simply tap in.
Croatia took control of the contest and were given a numerical advantage when Song struck Mandzukic on the back as Croatia began an attack, with referee Pedro Proenca showing no hesitation in brandishing a red card.
Cameroon's woes deepened within three minutes of the restart as the impressive Perisic struck.
Itandje's poor clearance found the Croatia midfielder, who surged down the left, outpacing the Cameroon defence, before executing a simple finish.
Mandzukic should have netted a third after being played in, but Nicolas Nkoulou applied enough pressure to put off the striker, who scooped his effort wide.
Half-time substitute Dany Nounkeu attempted a spectacular volley which flew well over as Cameroon tried to respond.
A Srna free-kick from the edge of the area went over before Danijel Pranjic's outswinging corner from the left was met by Mandzukic who was unchallenged as he headed the ball down and into the net.
Stephane Mbia shot narrowly over from long range before substitute Eduardo saw his shot saved weakly by goalkeeper Itandje.
The ball was parried to Mandzukic who tapped in.
Moukandjo spurned the chance of a consolation with five minutes remaining, curling wide with the Croatia goal gaping.
Ivan Rakitic fluffed an opportunity for a fifth at the other end before Pierre Webo's header bounced up and clear off the bar following Assou Ekotto's cross.
Assou Ekotto and Moukandjo squabbled in the aftermath, with the former throwing his head towards his team-mate in the closing moments in an unsavoury conclusion to the contest.