| Date: | 18–24 January |
| Edition: | 34th |
| Surface: | Hard (Indoor) |
| Location: | Istanbul, Turkey |
| Champs: |  Arthur Rinderknech |
| Champd: |  André Göransson / David Pel |
| After Year: | 2021 |
| After Name: | Amex-Istanbul Challenger II |
The 2021 Amex-Istanbul Challenger was a professional tennis tournament played on hard courts. It was the 34th edition of the tournament which was part of the 2021 ATP Challenger Tour. It took place in Istanbul, Turkey between 18 and 24 January 2021.
| Country | Player | Rank1 | Seed | |
|---|---|---|---|---|
 Colombia | Daniel Elahi Galán | 115 | 1 | |
 Brazil | Thiago Seyboth Wild | 117 | 2 | |
| France | Antoine Hoang | 121 | 3 | |
 Argentina | Facundo Bagnis | 125 | 4 | |
 India | Prajnesh Gunneswaran | 128 | 5 | |
 Italy | Lorenzo Musetti | 129 | 6 | |
 Slovakia | Jozef Kovalík | 131 | 7 | |
 Japan | Go Soeda | 134 | 8 |
The following players received wildcards into the singles main draw:
The following players received entry from the qualifying draw:
The following player received entry as a lucky loser:
See main article: 2021 Amex-Istanbul Challenger – Singles.
Arthur Rinderknech def. Benjamin Bonzi 4–6, 7–6(7–1), 7–6(7–3).See main article: 2021 Amex-Istanbul Challenger – Doubles.
André Göransson / David Pel def. 
Lloyd Glasspool / 
Harri Heliövaara 4–6, 6–3, [10–8].
