The French team, who were gold medallists at the recent world championships in Hamburg, were on top in the four legs and won in 1 hour 15 minute 07 seconds.
Switzerland won silver in 1:15:18, ahead of Belgium who rounded off the podium just 11 seconds behind.
After a quick exit from the water, it was a strong start for Belgium. Claire Michel, fifth in the women's event, made the pace on the bike section together with Frenchwoman Leonie Periault.
France, Belgium and Portugal went first into the second leg, with men's individual gold medallist Pierre Le Corre (FRA) keeping the rhythm and being caught on the run segment by silver medallist Fernando Alarza (ESP) and Belgium's Jelle Geens.
At the following handover, Olympic champion and six-time gold medallist Nicola Spirig (SUI) showed all her power to give Switzerland the lead on her leg, followed by Cassandre Beaugrand (FRA), who won bronze in the women’s event.
The gap Spirig created disappeared in the swim section of the fourth leg. Dorian Coninx (FRA) and Sylvain Fridelance (SUI) worked together until the Frenchman stretched away comfortably for gold.
Great Britain should have expected a podium spot but last-minute changes to the team proved disruptive. Beth Potter lost contact during the swim and Britain were never able to get back in touch, despite loud support from the crowd.
The mixed relay will be part of the programme for the first time at the Tokyo 2020 Olympic Games.