The Soudal Quick-Step rider crossed the goal line in 3hrs 32mins 03sec as he comfortably won the flat 156.1km stage around the greater Paris region.
Frenchman Arnaud Demare and Italian Alberto Dainese came second and third, respectively.
American rider Matteo Jorgenson (Visma-Lease a Bike) got the defence of his Paris-Nice title off to a strong start by collecting four seconds in time bonuses during the 156.1km stage.
With the final 20 kilometres seeing several attacks launched over undulating terrain, it was far from a simple finish for Merlier and the sprinters to operate.
But the last group to escape with Josh Tarling (Ineos Grenadiers), Matteo Trentin (Tudor) and Mattias Skjelmose (Lidl-Trek) present could only make it to the 2.4km to go.
“There’s always an extra pressure on you at the first race you do with a special jersey on your shoulders, but luckily, I managed to get the win just a couple of days after becoming European Champion, so all is good. The boys were again amazing today. It wasn’t easy, because I didn’t have the best feeling and I was also blocked behind that crash, but thanks to Warre I could make it back just in time for the sprint", said Merlier after the sprint.