South Africa's Sundowns hosted the first leg in Pretoria as the top-ranked clubs entered the competition at the last-32 stage.
The hosts set off to a blistering start, going 2-0 up inside the first six minutes, before KCCA's second half strike.
KCCA FC's coach Mike Mutebi, who had warned his opponents that his players could cause a shock, could not have predicted a worse start for his side.
Soumahoro Bangaly put Sundowns in front after just 2 minutes with Brazilian Ricardo Nascimento making it 2-0 to the South Africans just four minutes later.
However, the Ugandans frustrated the hosts, and their resilience was rewarded in the second half.
KCCA's goal came from in-form Geoffrey Sserunkuma in the 68th minute which could prove to be vital ahead of the return leg next weekend.
Click here for Champions League fixtures and results from the Caf website
On Saturday, record 8-time African champions Al Ahly of Egypt beat South African league leaders Bidvest Wits 1-0 in Cairo.
Centreback Ahmed Hegazy, who starred when Egypt finished Africa Cup of Nations runners-up last month, scored the winner on 57 minutes.
Former African title-holders Esperance of Tunisia and Wydad Casablanca of Morocco also used home advantage to build leads ahead of return matches next weekend.
Ferjani Sassi put Esperance ahead against Horoya of Guinea in Rades and restored the lead after Burkinabe Yacouba Mando levelled before half-time.
Fakhreddine Ben Youssef added a third goal for the two-time African champions with 15 minutes left.
Liberian William Jebor scored late to earn Wydad Casablanca a 1-0 win in Rabat over Mounana of Gabon, who had David Massamba sent off just before half-time.
Wydad, semi-finals losers to Zamalek of Egypt last season, squandered numerous scoring chances.
On a profitable day for north African clubs, 2015 Champions League runners-up USM Alger of Algeria defeated Rail Kadiogo of Burkina Faso 2-0 in Algiers.
The African Champions League holders Mamelodi Sundowns began the defence of their crown with a 2-1 win over Kampala Capital City Authority (KCCA) of Uganda on Friday, but conceded what could be a costly away goal.