Four-time winners, Mazembe, had to wait till the halfway mark at the mini-league stage to grab their first win in Group A, made possible by a goal in each half from Zambia captain Rainford Kalaba and Ghana-import Daniel Nii Adjei.
The victory is a huge boost for the DR Congo champions after an unfamiliar start at the last eight, and also shakes some pressure off Frenchman Patrice Carteron.
With the appointment of Mohamed Youssef, the man who guided his boyhood club, Al Ahly to the title in 2013 few days before the clash, Smouha were eyeing their second win at home at this stage.
Two chances for the hosts were squandered by Hany Shaban who headed wide on both occasions on 10th and 26th minutes before Mbwana Samata headed into the waiting hands of Mahdy Soliman from a Kalaba pass on 28 minutes in the first chance by the visitors.
On 40 minutes, Malian winger Adama Traore set up Kalaba, who shot past Soliman for the opener. The Lubumbashi-based club had gone 220-minutes without a goal in the premier continental club championship.
Smouha resumed stronger but failed in several bids for the equalizer. Seven minutes from time, Traore this time laid to Nii Adjei, who capitalised on poor defending by the homers rear and struck past Soliman to seal victory.
Mazembe moves to the summit of the group temporarily on five points, one more than El Hilal of Sudan who play as guests of Moroccan side, Moghreb Tetouane on Sunday in Tetouan.
In Group B, USM Alger made it three wins out of three and moved to the brink of a semis berth. Midfielder Kaddour Beldjilali broke the deadlock on 16 minutes by connecting home a pass from Mohamed Bellaili.
Mohamed Seguer doubled the lead on 22 minutes, from a Bellaili assist before Nathir Korichi reduced the deficit five minutes before the break.
USM Alger has nine points and are within a touching distance of a place at the semis, whilst fellows Eulma remain at the depth of the standings pointless.
24.7.2015 19H30 Smouha (Egypt) 0-2 TP Mazembe (DR Congo)
26.7.2015 21H30 Moghreb Tetouane (Morocco) vs El Hilal (Sudan)
24.7.2015 20H30 USM Alger (Algeria) 2-1 MC Eulma (Algeria)
25.7.2015 21H30 ES Setif (Algeria) vs El Merreikh (Sudan)