Pakistan, set 235 to win, finished on 167 all out as South Africa made light of the absence of premier fast bowlers Dale Steyn and Morné Morkel in winning with five overs to spare.
Man-of-the-match Hashim Amla made 81 - after being dropped before he reached double figures - and that was the cornerstone of South Africa's 234 for nine, a total the Proteas had no trouble in defending.
"Not many teams would have been able to get 234 against that bowling attack like we did," said South Africa captain AB de Villiers.
"A quick word for Chris Morris, who enjoyed a wonderful debut today."
Pakistan captain Misbah-ul-Haq, who top-scored for his side with 55, lamented the team's batting.
"We needed four-and-a-half an over but we could not rotate (the strike) in the middle. That score you could have chased down."
McLaren's return, which included a spell of four for five in 11 balls, saw him enjoy fresh success at an Edgbaston ground he'd once helped look after while with Warwickshire 2nd XI.
In 2007, the seamer took a hat-trick at Edgbaston for Kent as they won English county cricket's Twenty20 Cup.
Both Pakistan and South Africa needed to win this day/night fixture after losing their opening Group B matches to the West Indies and India respectively.
But defeat left Pakistan's hopes of a semi-final spot hanging by a thread. They will hope that the West Indies can beat India before they tackle their fierce sub-continent rivals on Saturday, also at Edgbaston.
"We must forget about the first two games, try to win that game (against India) and play positive cricket," Misbah said.