AFC Champions League Wrap: Elkeson, Muriqui put Evergrande in control
The defending champions took complete command of the tie in Osaka, and look set to progress to the quarter-finals after a devastating display.
Muriqui put the visitors ahead midway through the first half, only for Aria Hasegawa to level matters on the half-hour mark.
Elkeson restored Guangzhou's lead from the penalty spot after 34 minutes, and put them 3-1 ahead with another strike three minutes later.
Goals in the final 12 minutes from Gao Lin and Muriqui wrapped up the win, with next week's second leg looking like a formality.
Pohang Steelers, champions in 2009, also appear to be in the driving seat after a 2-1 win at Jeonbuk Motors in a clash between the K-League's top two.
They fell behind nine minutes into the second half to Lee Jae-Seong's effort, but were level four minutes later through Son Joon-Ho.
The visitors edged in front for the first time 16 minutes from time when Ko Mu-Yeoi struck, and the win will leave Pohang confident of progressing against their Korean rivals in the second leg.
Another side to enjoy a 2-1 success away from home were United Arab Emirates outfit Al Ain, who got the better of fellow Pro League side Al Jazira.
The pair met for the second time in six days following Thursday's 2-2 draw in the league, and the prolific Asamoah Gyan netted his 36th goal of the season in the 11th minute, with Omar Abdulrahman doubling the advantage four minutes later.
Musallem Fayez did pull one back for the hosts shortly before the hour-mark, but Al Jazira could not force the equaliser and will face a deficit in next week's second leg.
In the other tie to be played on Tuesday, Mukhtar Fallatah's 75th-minute strike earned Al Ittihad a 1-0 home win in their first leg against Saudi Pro League rivals Al Shabab.