Zverev is yet to drop a set at this year's tournament, while Tiafoe came from behind to defeat Aslan Karatsev on Thursday.
Having been plagued by injury since tearing all three lateral ligaments in his right ankle during a semi-final match against Rafael Nadal at last year's French Open, Zverev appears to be finding his stride on the ATP Tour once again.
The German recently became the only tennis player aged under 30 to rack up 350 career wins when defeating Roberto Carballes Baena in the final of the Madrid Open, while he has lost just eight games across four sets since winning two tie-breakers against Lloyd Harris in the opening round.
However, the 26-year-old will be acutely aware that Tiafoe represents a serious danger to his hopes of winning his first ever Grand Slam, even if his forthcoming opponent would openly admit that clay is not his strongest surface.
As such, Zverev will be expecting to win having regularly proved his worth on the red dirt in recent years. Indeed, he has reached at least the fourth round of the French Open in each of the past five years, suggesting he has a real chance of competing at the business end of the tournament, with his chances of triumphing significantly boosted by the absence of Nadal through injury.
For Tiafoe, on the other hand, Saturday's meeting with Zverev will be his first ever appearance at the third round of this tournament.
The 25-year-old only recorded his first ever win at the French Open by defeating Benjamin Bonzi in last year's opening round, having fallen at the first hurdle in each of his first six visits to Roland Garros.
However, there is little doubt that the American is entering his prime years after reaching the semi-finals of a Grand Slam for the first time in his career in his home country last September, and he will possess plenty of belief that he can cause an upset against Zverev this weekend.
Tiafoe forced 14 break points against Karatsev - winning six of them on his way to a four-set victory - suggesting he has every chance of causing the German plenty of issues in his own service games, which have proved a particular weak spot throughout Zverev's career.
Tournament so far
First round: vs. Lloyd Harris 7-6 7-6 6-1
Second round: vs. Alex Molcan 6-4 6-2 6-1
First round: Filip Krajinovic 6-3 6-4 6-2
Second round: Aslan Karatsev 3-6 6-3 7-5 6-2
Head To Head
Vienna Open (2021) - Final: Zverev def. Tiafoe 7-5 6-4
Beijing Open (2019) - Last 32: Zverev def. Tiafoe 6-3 6-2
US Open (2019) - Last 64: Zverev def. Tiafoe 6-3 3-6 6-2 2-6 6-3
Paris Masters (2018) - Last 32: Zverev def. Tiafoe 6-4 6-4
Cincinnati Masters (2017) - Last 32: Tiafoe def. Zverev 4-6 6-3 6-4
Wimbledon (2017) - Last 64: Zverev def. Tiafoe 6-3 6-4 6-3
Australian Open (2017) - Last 64: Zverev def. Tiafoe 6-2 6-3 6-4
Zverev clearly holds the edge over Tiafoe in terms of their head-to-head meetings, having won six times to the American's sole victory at the Cincinnati Masters six years ago.
However, they have played each other just once since the turn of the decade - when Zverev triumphed at the Vienna Open two seasons ago - and there is little doubt that Tiafoe has considerably improved during that timeframe.
In terms of Grand Slam meetings, Zverev has won on all three occasions, with their US Open clash in 2019 going the distance.
We say: Zverev to win in four sets
Although Tiafoe is seeded 10 places higher than Zverev, that is predominantly due to the German's recent injury problems and consequential fall in the ATP rankings.
Zverev is clearly a far more accomplished player on clay and we expect him to make it to the fourth round of the French Open for the sixth successive year. However, Tiafoe is growing in confidence on this surface and it would be a surprise if he did not manage to take his opponent to four or five sets on Saturday.