The 2021 Murcia Open was a professional tennis tournament played on clay courts. It was the 2nd edition of the tournament which was part of the 2021 ATP Challenger Tour. It took place in Murcia, Spain, between 27 September and 3 October 2021.
The following players received wildcards into the singles main draw:
The following players received entry into the singles main draw using protected rankings:
The following players received entry from the qualifying draw:
