The Springboks outscored the All Blacks six tries to four on Saturday (Sunday AEST) with Damian de Allende, Morne van den Berg, Malcolm Marx, Pieter-Steph du Toit, Kurt-Lee Arendse and Cameron Hanekom all going over.
New Zealand captain Codie Taylor scored the first try of the game, with Will Jordan, Ethan Blackadder and Beauden Barrett adding scores of their own.
The clash in the United States concluded New Zealand's eight-match, six-week tour of South Africa that was the first of its kind in 30 years.
The clash at the home of the NFL's Baltimore Ravens drew 68,173 spectators in a money-spinning exercise for both unions. The series began last month with New Zealand playing provincial opponents, before winning the first Test in Johannesburg, but South Africa took the next three to keep up their top ranking.
All Blacks coach Dave Rennie said his side had made strong strides towards next year's World Cup despite the series defeat to the reigning world champions.
"We'll wake up tomorrow and know we're moving in the right direction," he said.
"We scored 17 tries in the four Tests. We're in a good place but tonight will hurt.
"I thought we defended pretty well throughout the series, but got beaten by some of their flash boys tonight."
Rennie said the Springboks were setting the benchmark one year out from next year's World Cup in Australia, where South Africa will be seeking a third successive triumph.
"They're where we want to get to. We've been together for 10 or 11 weeks, while they have a lot of experience. I'm not sure if all of those guys will still be here this time next year," the former Wallabies coach added about an ageing Springboks team.
"You have to give it to them. They've got better and better as the tour has gone on.
"But the work ethic has been excellent, the guys have been great and I knew coming here we'd grow."
New Zealand next compete in the Nations Championship in November where they have Tests in Scotland, Wales and England. They kick off their World Cup against Chile in Perth on October 2 next year.
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