Pollock took five for 23 as Pakistan were bowled out for 153. AB de Villiers and Jacques Kallis hit half-centuries as South Africa cruised to a nine-wicket victory with 21.4 overs to spare. South Africa won the series 3-1, with one match rained off.
"We finished on a high note," said Pollock. "We're going to head off to the World Cup with a lot of confidence."
Pollock was named man of the match and clinched his third man of the series award of the South African summer. He took the award for both the Test and one-day series against India earlier in the season.
"I don't take it for granted," he said. "I'll keep working on my game. All credit to the team. The bowlers have been superb throughout. If we can continue with that and the batting form we've shown it will be great."
Pollock bowled unchanged with the new ball and took the first five wickets with a superb exhibition of accurate seam and swing bowling.
Pakistan hopes were raised briefly when South African captain Graeme Smith was caught behind off Mohammad Asif for nought.
Asif and Rao Iftikhar Anjum bowled well and forced De Villiers and Kallis on to the defensive as the pitch seemed to gain extra life under the floodlights.
But then Kallis hit Iftikhar for six, four and four off successive balls and followed up with two boundaries off the next two deliveries he faced, from Asif in the next over, as South Africa took control.
Both batsmen finished with 71 not out as they put on an unbeaten 155 off 175 balls for the second wicket.
It was the second successive crushing win for South Africa, who won by ten wickets in the fourth match in Cape Town last Sunday. "The last two games were unbelievable," said Smith.
"Shaun has led us superbly with the ball and the guys have backed him up in the field."
Smith said: "Our confidence is high but the guys have worked hard for this victory and our feet are still firmly on the ground."
Pakistan captain Inzamam-ul-Haq bemoaned a poor batting performance on a good pitch and admitted there was much to do before the World Cup. "We've got two weeks. We'll look at our weaknesses and God willing we will play well at the World Cup."
On a pitch with the most bounce seen in the series, Pakistan were in trouble from the first over when Pollock had Mohammad Hafeez caught behind.
Imran Nazir went on the attack to make 22 off 22 balls. He hit Pollock for a six over midwicket before an attempted repeat sent the ball high in the air for Pollock to take a return catch.
Pollock followed up with the wickets of Pakistan's three senior batsmen. He bowled Younis Khan, trapped Mohammad Yousuf leg before with a ball which swerved back into the batsman, and had Pakistan captain Inzamam-ul-Haq caught at second slip.
Kamran Akmal fell for 22 when he pulled powerfully against Charl Langeveldt and Ashwell Prince dived to his right in front of the square leg umpire to hold a reflex catch. At that stage Pakistan, who won the toss, were 83 for six.
Only Shoaib Malik, who made 43 not out off 70 balls, provided sustained resistance to the South African attack.
South African wicketkeeper Mark Boucher, who equalled the world record when he held six catches in the fourth match in Cape Town, followed up with five catches as South Africa secured a second successive win by a large margin.
The result meant South Africa reinforced their ranking as the second-best one-day side in the world behind Australia, with the gap closing following Australia's recent defeat by England in the triangular series in Australia.
It was the last competitive cricket for both teams ahead of next month's World Cup.
Pakistan 153 in 40.5 overs (Shoaib Malik 43 n o, Kamran Akmal 22, Imran Nazir 22; Pollock 5 for 23, Kallis 2 for 19, Andre Hall 1 for 25) lost to South Africa 156 for 1 in 28.2 overs (AB de Villers 71 n o, Jacques Kallis 71 n o; Mohd Asif 1 for 24) by 9 wickets
Series Result: South Africa wrap-up the 5-game ODI series by 3-1(3rd tie at Port Elizabeth was abandoned)