After beating Alpha 2-0 away from home in their opening match, Olimpia were never troubled by their Guyanese opponents at the Estadio Tiburcio Carias Andino.
The reigning Honduran champions opened the scoring on 19 minutes through Antony Lozano before Oliver Morazan doubled his side's advantage five minutes later.
Two goals either side of the half from Fredickson Elvir put the game out of reach for Alpha with Lozano scoring again before Elvir completed his hat-trick 16 minutes from time.
The result leaves Alpha rooted to the bottom of the group and unable to progress from the group stages while Olimpia overtake the Portland Timbers to go top.
Waterhouse also enjoyed a big win as they eased past Tauro FC 4-1 in a Group Four encounter.
Knowing a win would see them move to the top of the group, the Jamaican side started brightly through Jermaine Anderson and never looked back.
Damarley Samuels put the hosts two to the good just after the half-hour mark before Anderson scored his second.
A goal to Jose Garces gave Tauro a glimmer of hope in the last 30 minutes but it proved to be a mere consolation as Nicko Williams sealed the win in injury time.
In the day's other match, Costa Rican side Alajuelense scraped past Chorrillo 1-0 with an early Armando Alonso strike enough to move them to the summit of Group Six.
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