The Deceuninck-QuickStep rider beat Jakob Fuglsang (Astana) into second, while Diego Ulissi (UAE Team Emirates) took third on the line.
Michał Kwiatkowski (Team Sky) was at the front of the race in the final kilometre and was then joined by Ulissi and Tim Wellens (Lotto–Soudal).
Fuglsang came forward, attacked and went clear.
Alaphilippe, who won the Strade Bianche last month, started the chase with 250m to go and Fuglsang was unable to hold on.
“This race is something special for me. I always seem to finish on the podium whenever I come here,” said Alaphilippe.
“It was all about feelings today and going with your feelings. It was nervous out there but I was well supported.”
View more results below.
1. Julian Alaphilippe (Fra) Deceuninck-QuickStep 4:55:15
2. Jakob Fuglsang (Den) Astana Pro Team
3. Diego Ulissi (Ita) UAE Team Emirates +0:00:06
4. Bjorg Lambrecht (Bel) Lotto Soudal +0:00:08
5. Maximilian Schachmann (Ger) Bora-Hansgrohe
6. Bauke Mollema (Ned) Trek-Segafredo
7. Patrick Konrad (Aut) Bora-Hansgrohe
8. Michael Matthews (Aus) Team Sunweb
9. Jelle Vanendert (Bel) Lotto Soudal +0:00:11
10. Enrico Gasparotto (Ita) Dimension Data
Watch the highlights of the 2019 La Flèche Wallonne below.