The run was shortened considerably due to strong winds on the mountain, with the start lowered to the dramatic Hundschopf (Dog's Head) jump.
Odermatt attacked from the off with bib number seven, crossing the finish in one minute 33.14 seconds.
Austria's Vincent Kriechmayr finished a distant second, his time 0.79 slower, with Italy's Giovanni Franzoni third from a 28th start and a day after taking his first World Cup win in the super-G.
Odermatt, now on 52 World Cup victories, won two downhills in Wengen in 2024 and another in 2025.
Switzerland's reigning downhill world champion Franjo Von Allmen, pushed off the podium by Franzoni going 0.03 quicker, was fourth, with teammate Alexis Monney fifth and Italy's Dominik Paris sixth.
Chile's Henrik Von Appen, a veteran of three Olympics and heading for another at the age of 31, also caught the eye by starting 50th of 56 and finishing 16th.
Odermatt leads the overall, downhill, super-G, and giant slalom World Cup standings and is the outstanding men's Alpine skiing medal prospect for next month's Milano Cortina Winter Olympics.
The downhillers move on to Kitzbuehel's famed Streif next weekend before a final downhill in Crans-Montana ahead of the men's Olympic races in the Italian resort of Bormio.
