Marchand is the Olympic hosts' big hope after last year demolishing Michael Phelps' 15-year-old world record in a phenomenal 4min 2.50sec.
The 22-year-old, trained by Phelps' old coach Bob Bowman, had not dipped under 4:10 this year as a number of his rivals did, piling on the pressure.
He rose to the occasion on day two at a packed La Defense Arena to touch in 4:08.30 as a raucous crowd went wild, more than a second clear of Britain's Max Lichfield and two seconds ahead of Japanese veteran Daiya Seto.
In an upset, American defending champion Chase Kalisz failed to reach the final, ending his bid to make the podium for a third time after also winning silver at Rio 2016.
"It was almost like a football stadium but in a pool. Everyone was chanting my name, it was crazy," said Marchand, who is gunning to end a 12-year French gold medal drought in the pool.
"I think I was prepared. I was able to stay in my performance. I had a very strong 250m and then I relaxed a little.
"If I can free myself as much as possible from my body, from my mind, it will be great. I think it'll be fun," he added of Sunday's evening final.
At the 2021 Olympics, France took home just one swimming medal, Florent Manaudou's silver from the 50m free. They haven't won gold since London in 2012, when they collected four.
Marchand will also swim the 200m medley and 200m butterfly.
Defending 200m champion Titmus was back in the pool a day after taking out the 400m title ahead of Summer McIntosh and Katie Ledecky.
She showed few signs of tiredness, easing into the semi-finals third fastest behind pace-setting teammate O'Callaghan (1:55.79).
Calm
Titmus shattered O'Callaghan's world record last month at the Australian trials to set a new best of 1:52.23.
O'Callaghan also went under her previous world record in coming second, making the pair overwhelming favourites for gold on Monday.
"Definitely hard to back up after last night, but I think I tried to stay as calm as I could last night and try and forget about what happened this morning really," said Titmus.
"On to another day, 400's done now, so 200's the focus."
David Popovici was fastest through the men's 200m freestyle heats, touching in 1:45.65 ahead of Lithuania's Danas Rapsys and Belgium's Lucas Henveaux.
The Romanian, who burst on the scene by winning the 100-200m freestyle double at the 2022 world championships and smashed the 100m world record later that year, is in top form after recently clocking the fifth fastest time ever.
Germany's Lukas Martens, fresh from winning the 400m gold medal, also qualified for the semi-finals, as did reigning world champion Hwang Sun-woo of South Korea.
But China's Pan Zhanle missed out, and by a long way, with the current 100m world record holder nearly four seconds adrift.
In other heats, South Africa's Tatjana Smith surged home in 1:05.00 in the women's 100m breaststroke, outpacing Chinese world champion Tian Qianting and Ireland's Mona McSharry.
American world record holder Lily King, the Rio gold medallist who won bronze in Tokyo, was fifth fastest.
Hungary's Hubert Kos (52.78) led the way into the men's 100m backstroke semi-finals.
The United States' Ryan Murphy, who won gold at Rio 2016 and bronze in Tokyo three years ago, was fourth fastest, with Italian world record holder Thomas Ceccon 12th.
Along with the men's 400m medley, there are two other finals on Sunday, headlined by 100m breaststroke king Adam Peaty's bid to match Michael Phelps and win three consecutive gold medals in the same event.
American Gretchen Walsh is the red-hot favourite to take out the women's 100m butterfly crown after smashing the world record at the US trials.
