The 2021 Zagreb Open was a professional tennis tournament played on clay courts. It was part of the 2021 ATP Challenger Tour. It took place in Zagreb, Croatia between 10 and 16 May 2021.
| Country | Player | Rank1 | Seed | |
|---|---|---|---|---|
 Argentina | Federico Coria | 92 | 1 | |
 Spain | Pedro Martínez | 95 | 2 | |
 Slovakia | Andrej Martin | 109 | 3 | |
 Japan | Yasutaka Uchiyama | 110 | 4 | |
| Pedro Sousa | 113 | 5 | ||
 France | Benjamin Bonzi | 115 | 6 | |
 Bosnia and Herzegovina | Damir Džumhur | 118 | 7 | |
 Brazil | Thiago Seyboth Wild | 126 | 8 |
The following players received wildcards into the singles main draw:
The following player received entry into the singles main draw as an alternate:
The following players received entry from the qualifying draw:
See main article: 2021 Zagreb Open – Singles.
Sebastián Báez def. 
Juan Pablo Varillas 3–6, 6–3, 6–1.See main article: 2021 Zagreb Open – Doubles.
Evan King / Hunter Reese def. 
Andrey Golubev / Aleksandr Nedovyesov 6–2, 7–6(7–4).