Briton Tahnée Seagrave and world champion Loic Bruni triumphed in the 2019 season opener at Maribor with Atherton and Pierron determined to hit back in Scotland.
Rain and wind saw Bruni and Seagrave both suffer dramatic crashes before the race itself with the latter forced out entirely, after she injured her collarbone.
The women went first with Italian Veronika Widmann and German Nina Hoffmann both posting great times in wet, blustery conditions that swept across the mountain.
World champion Atherton, though, has won six World Cup titles and used her experience to record a superb 5:15.560 with leading qualifier Tracey Hannah last.
Australian Hannah was up at the third split, but lost time to go behind at the fourth with a fast last section not enough to deny Atherton her 38th World Cup victory that puts her within three of the women's all-time 41 mark set by Anne-Caroline Chausson of France.
Atherton, 31, said: "That was the most nail-biting thing ever. I am absolutely buzzing - a win at Fort William is special enough without doing it for the first time for Atherton Bikes. That is all I have been thinking about all winter. The weather is really horrific. It is really hard to concentrate on your bike set-up and your line choice. Everyone is covered in mud. It is carnage. It is the worst weather I have ever experienced."
Hannah, 30, added: "Rachel is a beast on Fort William, so I had to really have a confident strong mindset from the beginning. I had to go as hard as I possibly could."
The men followed in conditions that turned for the better with Frenchman Bruni posting a great early time considering how bad his crash had been in qualifying.
Aaron Gwin suffered a bad early crash to wreck his hopes leaving Canadian Finn Iles to beat out team-mate Bruni with Troy Brosnan the next in the leader's seat.
Pierron, though, drew on his 2018 success to pull out a brilliant run and take a lead which compatriot Loris Vergier could not better for his second Fort William win.
Pierron, 23, revealed: "I struggled a lot on the first run and we did some adjustments on the bike so I want to thank a lot my family and team. It is awesome. I felt good on track and had a lot of fun."
1. Rachel Atherton GBR 5:15.560
2. Tracey Hannah AUS +1.611
3. Nina Hoffmann GER +8.822
4. Marine Cabirou FRA +13.374
5. Veronika Widmann ITA +15.735
UCI MTB World Cup women's downhill overall:
1. Rachel Atherton GBR 430 points
2. Tracey Hannah AUS 400
3. Marine Cabirou FRA 290
4. Nina Hoffmann GER 285
5. Tahnée Seagrave GBR 230
Fort William men's downhill result:
1. Amaury Pierron FRA 4:28.578
2. Troy Brosnan AUS +3.582
3. Loris Vergier FRA +3.631
4. Finn Iles CAN +7.203
5. Danny Hart GBR +7.518
UCI MTB World Cup men's downhill overall:
1. Troy Brosnan AUS 350 points
2. Amaury Pierron FRA 330
3. Loic Bruni FRA 301
4. Danny Hart GBR 292
5. Loris Vergier FRA 215