The Tunisians, winners of this competition in 2006 and runners-up two years later, produced a dramatic finish to stun the Zambian champions and move top of their pool.
Things began badly for Sahel in the Stade de Olympique de Sousse when defender Ghazi Abderrazzak put through his own net in the seventh minute.
The hosts pulled level after 20 minutes, Baghdad Bounedjah tucking away a penalty, but they went into half-time trailing after Evans Kangwa had given Nkana the lead once more.
Kalil Bangoura levelled matters with a strike eight minutes after the break, but Derrick Mwansa's spot-kick 11 minutes from time looked to have given the visitors their first win in this year's group stage.
A thrilling end to the game saw the hosts snatch victory, however, as Lasaad Jaziri produced a third equaliser a minute later, and Bangoura won it five minutes from time to move Sahel to five points from their three fixtures, while Nkana have just one point to show for their efforts thus far.
In Group A, Leopards de Dolisie moved joint top of their pool with Cotonsport, after a 2-1 success away at Real Bamako.
The visitors hit the front on 36 minutes thanks to Cesaire Gandze's strike, but were pegged back midway through the second half when Ali Badra Sylla found the net.
Leopards, winners in 2012, snatched all three points late on, Kader Bidimbou coming up with the winning goal two minutes from time to move his side level on four points with Cotonsport having played twice, while ASEC and Bamako are locked on two points from their three games to date.
