The Green Shirts, chasing a 165-run target set by the Proteas, managed to win with four wickets in hand with eight balls to spare.
Babar Azam (44) and Mohammad Rizwan (42) anchored the team with their solid performances.
Hasan Ali (20), Mohammad Nawaz (18), Haider Ali (15), Faheem Ashraf (10) also lent a hand.
South African bowler Tabraiz Shamsi tried throughout to dismantle the side, managing in the effort to grab four wickets.
Bjorn Fortuin and Dwaine Pretorius grabbed one each of the only two other wickets the visitors were able to get.
South Africa innings
South Africa set the score at a loss of eight wickets. The side’s top scorers were David Miller (85 not out) and Janneman Malan (27).
From the Pakistan side, debutant Zahid Mahmood emerged as the top wicket-taker with a haul of three. Mohammad Nawaz and Hasan Ali took two each and Usman Qadir took one.
Pakistan won the first match by three runs while South Africa took the second by six wickets, both also in Lahore.
Mohammad Rizwan becomes first-ever Pakistani wicket-keeper to score 100 in T20I
With the series locked at one-all, Pakistan brought in leg-spinner Zahid Mahmood for his international debut.
Also included were batsman Asif Ali and medium pacer Hasan Ali. The trio replaced Khushdil Shah, Iftikhar Ahmed and Haris Rauf.
South Africa brought back Bjorn Fortuin for Glenton Stuurman.
Pakistan: Babar Azam (capt), Haider Ali, Hussain Talat, Asif Ali, Mohammad Nawaz, Faheem Ashraf, Mohammad Rizwan, Shaheen Afridi, Hasan Ali, Usman Qadir, Zahid Mahmood
South Africa: Heinrich Klaasen (capt), Reeza Hendricks, Janneman Malan, David Miller, Andile Phehlukwayo, Dwaine Pretorius, Tabraiz Shamsi, Lutho Sipamla, Pite van Biljon, Bjorn Fortuin, Jon-Jon Smuts