Jennings, 25, was out for 48 on the fourth morning of the third Test against the Proteas, meaning he averages only 15.3 in six innings.
"Even though he got 48, there were a lot of edges," said Smith.
"If I was a selector I'd be thinking it was time to make a change with the West Indies and then the Ashes coming up."
England play one more Test against South Africa, followed by three against the West Indies before they defend the Ashes down under.
Johannesburg-born Jennings was 34 not out overnight at The Oval, having survived a dropped catch and successfully overturned an lbw decision on the third day.
He added 14 to his score before fending a short delivery from Kagiso Rabada to gully.
Speaking on Test Match Special, Smith - who led South Africa to two Test series wins in Australia - added: "Should England give another player time to settle in?
"The way that Jennings plays, I think Australia might be quite a scary place for him.
"It's not easy. These are people's lives and they're working hard, but I think South Africa would love Jennings to play in the final Test match.
"If you had to ask them they would say: 'Please pick him.'"
Jennings' struggles are the latest in an ongoing problem for England, who have tried 11 different opening partners for Alastair Cook since Andrew Strauss retired in 2012.
Some have had success - Adam Lyth and Sam Robson made centuries, while Haseeb Hameed impressed in India before suffering an injury and struggling for form with county side Lancashire.
Durham left-hander Jennings, who replaced Hameed in India, also made a century on his Test debut, but has since passed 50 only once in nine innings.
If he is removed from the England side, his most likely replacement would be Surrey's Mark Stoneman, who is the third highest run-scorer in County Championship Division One this season.
"I can't say if Stoneman is better, I haven't seen enough - but if they think there is potential then I would give him a go," said Smith.
An Ashes series in Australia will be a "scary" proposition for England opener Keaton Jennings, says former South Africa captain Graeme Smith.