Mweene's late heroics in this Africa Cup of Nations Group C clash on Friday cancelled out Emmanuel Emenike's goal with Nigeria's John Obi Mikel failing to convert a first-half penalty.
The stalemate left defending champions Zambia and Nigeria tied at the top of the mini-league, with Burkina Faso and Ethiopia playing later.
Nigeria coach Stephen Keshi made three changes.
In came Chelsea winger Victor Moses, making his Afcon debut after missing the 1-1 draw with Burkina Faso with a hamstring injury.
Joining Moses were Lazio midfielder Ogenyi Onazi and Fegor Ogude.
Fenerbahce defender Joseph Yobo dropped to the bench after a late ankle injury, with goalkeeper Vincent Enyeama taking over his captain's armband, Dynamo Kyiv striker Brown Ideye was also out, while Celtic defender Efe Ambrose was suspended.
For Zambia, defender Emmanuel Mbola and Southampton striker Emmanuel Mayuka were called up for Hichani Himonde and Collins Mbesuma, the scorer in the 1-1 stalemate with Ethiopia.
Chisamba Lungu, who suffered an ankle injury when floored by Ethiopian goalkeeper Jemal Tassew, won his battle to be fit for this sixth Nations Cup meeting between the two sides.
For the Zambians this clash on the threadbare Mbombela Stadium pitch represented the chance to avenge defeats to Nigeria in Angola in 2010 and in the 1994 final, the last of Nigeria's two titles.
Hervé Renard's men started ambitiously, but Nigeria's defence held firm as the title-holders struggled to capitalise on all their possession.
On 25 minutes, Zambia had a lucky escape when defender Davies Nkausu felled Ahmed Musa in the box, with Egyptian referee Ghead Grisha pointing to the spot.
Mikel stepped up, but his far-from-vintage low effort went the wrong side of Mweene's right post.
On the attack
Zambia ended the first half as they'd begun it, on the attack, yet unable to land a sucker punch.
A more assured Nigeria emerged after the restart, and deservedly took a 57th-minute lead when Emenike raced on to Mikel's neat through pass. He controlled the ball well before shooting low into the left hand corner of Mweene's net.
The Spartak Moscow striker was doubling his tally in South Africa, having scored in Nigeria's first game.
That sparked Renard to alter his line-up, Mbesuma and Mulenga Mukuka coming on for captain Christopher Katongo and Lungu. Soon after, Isaac Chansa came off for Jonas Sakuwaha as Renard strengthened his attack.
Mweene then saved Zambia's day.
The keeper, who regularly takes penalties for Free State Stars and converted his effort in last year's Afcon final shoot-out, stepped up to slot home a spot kick awarded harshly when Onazi tangled with Mayuka in the box. – Sapa