Congo Brazzaville-born Julsy Boukama-Kaya scored in each half for the home side before Brazilian Fabricio Simoes finished off the visitors with a penalty nine minutes from time.
Libolo lead Group C on goal difference from Zesco with each having six points from four matches.
Al Hilal Obeid of Sudan and Smouha of Egypt, who play late Tuesday, have four points each in a mini-league where all the matches bar one have ended in home victories.
Boukama-Kaya shared the individual honours with former Angola goalkeeper Landu Mavanga, who pulled off a string of superb saves.
The Congolese goal poacher turned inside the box and fired the ball wide of Zesco goalkeeper and captain Jacob Banda into the roof of the net on nine minutes.
After Zesco had pressed continuously during the second half, Boukama-Kaya pounced on a rebound to double the lead after 77 minutes.
When Zambian Daut Musekwa struck an opponent in the throat, the Angolan club were awarded a penalty which substitute Simoes calmly converted nine minutes from time.
Horoya of Guinea climbed two places to first in hotly-contested Group D by snatching a late 1-0 home victory in Conakry over bottom club Mounana of Gabon.
Sekou Camara rifled a rebound into the net on 81 minutes to give his team victory and eight points from four matches.
The Guineans have two points more than SuperSport United of South Africa and title-holders TP Mazembe of the Democratic Republic of Congo, who fought a dour 0-0 draw near Pretoria.
Billed as the highlight of matchday 4 in the African equivalent of the Europa League, the disappointing game was dominated by defences with the goalkeepers rarely tested.
SuperSport, who play Orlando Pirates in the South African FA Cup final this Saturday, kept seven-goal leading Confederation Cup scorer Jeremy Brockie on the bench for 45 minutes.
The introduction of the New Zealander for the second half in place of Zimbabwe defender Onismor Bhasera had minimal impact, however.
Every Group A match has produced a home win with Rivers United of Nigeria maintaining the trend by defeating Kampala Capital City Authority of Uganda 2-1 in Port Harcourt.
Goals from Bernard Ovoke and Frederick Obomate gave United a 2-0 lead after 15 minutes on a rain-drenched pitch and Geoffrey Sserunkuma reduced the deficit on the stroke of half-time.
Former Confederation Cup winners FUS Rabat of Morocco, Rivers and KCCA have six points and Club Africain of Tunisia three.
Club Africain host FUS near Tunis later Tuesday seeking revenge for a 2-1 loss in Morocco.
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