Guerrero tormented visiting Danubio at Arena Corinthians in Sao Paulo, scoring once in the first half before completing his hat-trick with two more goals after the interval.
The resounding victory saw Corinthians improve to 12 points from four Group Two fixtures, six clear of Sao Paulo and reigning champions San Lorenzo, who won 1-0 earlier on Wednesday.
Corinthians took a 27th-minute lead in sensational fashion via Jadson, who curled a free-kick into the top corner of the net.
Guerrero doubled the home side's advantage seven minutes later, diving low to head Elia's cross past Danubio goalkeeper Franco Torgnascioli.
Corinthians continued where they left off in the second half after Guerrero outmuscled his opponent and unleashed a powerful volley for his second goal of the match.
Guerrero netted his third in the 68th minute, when he managed to get a boot to Jadson's free-kick - taking his tally to eight goals in six matches in all competitions.
Danubio ended the match with 10 men after Matias de los Santos saw red for a second bookable offence six minutes from time.
Meanwhile, San Lorenzo joined Sao Paulo on six points thanks to a 1-0 win over their group rivals in Buenos Aires.
Uruguayan forward Martin Cauteruccio's 71st-minute strike was all that separated the teams as San Lorenzo kept their qualification hopes alive.
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