Rolando Blackburn struck a hat-trick for Comunicaciones as the Guatemalan club stormed to the top of Group Eight, while Waterhouse defeated Tauro 2-1 to claim first position in Group Four.
Comunicaciones blitzed Bayamon in the opening half hour on Thursday, scoring three times, including two goals to Blackburn, while the Panamanian striker added his third just two minutes after half-time.
The Guatemalans missed out on qualifying for the knockout stages of last season's Champions League, finishing six points behind Toluca of Mexico, but William Coito's team gave themselves every chance of progressing this term with a big win at home.
Comunicaciones took the lead in the ninth minute when Jairo Arreola collected an initial right-wing cross on the left-hand side of the box and drilled his pass back across goal for Blackburn to tap in.
The home side had the ball in the back of the net again in the 20th minute when Arreola drilled his shot past Bayamon goalkeeper Maximiliano Torlacoff but the goal was ruled out for a foul.
Comunicaciones did not have to wait much longer for their second goal, however, as Agustin Herrera struck a minute later, finishing off left-back Jorge Aparicio's cross.
Bayamon's right-hand side struggled in the opening half hour and Comunicaciones took advantage again in the 28th minute.
The home team's captain Jose Contreras found space on the left and chipped the ball to the back post for Blackburn to score with his head.
Blackburn effectively wrapped up the win for Coito's side in the 47th minute, getting his head to a corner, after Torlacoff came off his line but missed the ball.
In Panama, local club Tauro failed to complete a late comeback against Waterhouse.
The visitors from Jamaica had hit the front in the second minute through a brilliant free-kick from Romario Campbell and doubled their advantage 17 minutes later when Upston Edwards' driving run set up Damarley Samuels.
But Tauro surged in the second half with Jair Renteria scoring with five minutes left, converting the rebound after Christian Lopez hit the bar.
Rolando Palma's team could not find an equaliser, however, as Waterhouse won on their continental debut.
