Hamilton, along with teammate Michael Matthews, was part of an elite selection on the final climb of the day up to Chiroubles, as the first real general classification battle took shape.
Primož Roglič (Jumbo-Visma) saw the perfect moment to launch an attack within the final five kilometres and successfully held off the chasers by 12 seconds to take the day’s victory and move into the race lead.
Hamilton was part of the chasing group that closed down Roglič's advantage in the final kilometre, finishing sixth on the day.
The Victorian now sits a minute and nine seconds down on the new race leader in what is the 25-year-old’s first WorldTour outing of the season for Team BikeExchange.
“I think it was a good day for the team," said Hamilton, "it was quite a hard day and we had two of us there in the final, right up until one kilometre to go. We would have preferred to win of course but Roglič saw a good opportunity and he is one of the strongest bike riders in the world, so there was not much we could do then.
“I think he found a really good moment, and when a guy like that gets a small gap it is very hard to bring him back. It is one of those things, I was in the position that I was in and with that we did what we could.”
Hamilton is just one of many Australians looking for a good overall result at the race. Jack Haig (Bahrain Victorious) finished 12th, just four seconds behind the Hamilton group, while Ben O'Connor (AG2R-Citroen) finished 28th, 16 seconds in arrears. Giro d'Italia runner-up Jai Hindley (Team DSM) finished 53 seconds down on Roglič.
Paris-Nice continues tonight from 12.15am AEDT with Stage 5, a 203 kilometre stage from Vienne to Bollène primarily through the Rhône Valley, as the peloton traverses a flat course with a bunch sprint in Bollène looking likely.