The 2022 Winston-Salem Open was a men's tennis tournament play on outdoor hard courts.

It was the 53rd edition of the Winston-Salem Open (as successor to previous tournaments in New Haven and Long Island), and part of the ATP Tour 250 Series of the 2022 ATP Tour.

It took place at Wake Forest University in Winston-Salem, North Carolina, United States, from August 21 through August 27, 2022.

The following players received wildcard entry into the singles main draw: The following players received entry using a protected ranking: The following players received entry from the qualifying draw: The following players received entry as lucky losers: † Rankings are as of 15 August 2022.

The following pairs received wildcard entry into the doubles main draw :