The five-time African champions overtook the benchmark set 18 years ago by ASEC Mimosas of the Ivory Coast when they overwhelmed CR Belouizdad of Algeria 7-0 in Abidjan.
A few hours after Mazembe completed their destruction of Club Africain, the record was poised to be broken again as Al Ahly of Egypt charged to a 5-0 half-time lead over Simba SC of Tanzania.
But the eight-time African champions failed to score during a goalless second half in the Mediterranean city of Alexandria.
Mazembe ran riot in Lubumbashi just 14 days after suffering a three-goal hiding away to surprise Group C pacesetters CS Constantine of Algeria.
The home side netted four times in each half in the mining town with Kevin Mondeka, Jackson Muleka and veteran Tresor Mputu scoring two each and Mika Miche and Elia Meschak one.
Constantine top the table with six points, Mazembe have three and Club Africain none in a section reduced to three clubs after Ismaily of Egypt were disqualified for crowd violence.
If Mazembe avoid defeat away to Club Africain in Tunis on February 12 they and Constantine will secure quarter-final places.
Mazembe are among the favourites to win the Champions League along with trophy-holders Esperance of Tunisia, Wydad Casablanca of Morocco and Ahly.
Wydad win away
Amr Elsolia, Tunisian Ali Maaloul and Nigerian Junior Ajayi scored as Ahly swept into a three-goal lead and a Karim Walid brace stretched the advantage to five goals by the break.
It was the second successive match in which Simba conceded five goals, raising doubts about their ability to go any further in the competition.
Ahly, runners-up in the last two editions, top Group D with seven points, V Club of DR Congo have four, Simba three and JS Saoura of Algeria two.
Saoura came from two goals behind to draw 2-2 with V Club in Kinshasa where Sid Ali Yahia-Cherif equalised one minute from time.
Wydad became the first side to win away in Group A with a first-half penalty converted by Mohamed Nahiri earning a 1-0 victory over lacklustre Lobi Stars of Nigeria in Enugu.
The Moroccans had a genuine penalty appeal rejected before Mohamed Ounajem was fouled and Nahiri sent Olufemi Kayode the wrong way from a 19th-minute spot-kick.
Ahmed Tagnaouti of Wydad was the busier goalkeeper and did well to push away a Yaya Kone header before half-time on a scorching afternoon in southeastern Nigeria.
Wydad squandered a chance to increase their lead midway through the second half as Kayode saved another penalty, taken by Ounajem.
Mamelodi Sundowns and Wydad have six points with the South Africans occupying first place on head-to-head records having won 2-1 when the clubs met in Pretoria last month.
ASEC Mimosas of the Ivory Coast and Lobi have three points each and need matchday 4 wins against the teams they were beaten by this weekend to get back in contention.
Guinean outfit Horoya AC were rewarded for spending a week in Zimbabwe preparing to play FC Platinum when they won 1-0 thanks to a 51st-minute penalty from Marius Assoko in Bulawayo.
Orlando Pirates of South Africa and Esperance, who played a drab 0-0 draw in Soweto, have five points each in Group B, Horoya four and Platinum one.