Vincent Luis of France picked up his first win of the season in the series final in Rotterdam but third place was enough for Mola, who went into the race with a 340-point lead over compatriot Javier Gomez, to defend his crown.
Norwegian Kristian Blummenfelt was second, lifting him two places in the season standings to third.
Gomez came in fourth with Brownlee fifth in Rotterdam, leaving the two-time Olympic medallist sixth for the season.
Mola recorded his best swim of the season to trail the leader at that stage, Richard Varga, by 26 seconds.
Brownlee was eight seconds off the lead at that point despite swimming without goggles, and with the cold, wet weather suiting him he was in the leading group early in the bike ride.
The trailing pack group containing Mola made up 20 seconds as the two groups merged, and as the run began Brownlee and Blummenfelt were followed by Gomez and Luis.
Mola was going along nicely in fifth and before long he caught the leaders, with Brownlee dropping off the pack early in the final lap as Mola pushed through for series victory.
Flora Duffy retained her world title in style by racing to victory in the women’s event, Britain’s Jess Learmouth came third.
Bermudan Duffy only needed to finish in the top seven to seal another triumph but she burst clear of Learmouth and American Katie Zaferes on the 10km run. Learmouth came home third.