The 2018 Winston-Salem Open was a men's tennis tournament played on outdoor hard courts. It was the 50th edition of the Winston-Salem Open (as successor to previous tournaments in New Haven and Long Island), and part of the ATP World Tour 250 Series of the 2018 ATP World Tour. It took place at Wake Forest University in Winston-Salem, North Carolina, United States, from August 19 through August 25, 2018. It was the last event on the 2018 US Open Series before the 2018 US Open.
| Country | Player | Rank* | Seed | |
|---|---|---|---|---|
 Belgium | ||||
 Spain | 13 | 2 | ||
 United Kingdom | Kyle Edmund | 16 | 3 | |
 Italy | 22 | 4 | ||
 Bosnia and Herzegovina | ||||
 Korea, Republic of | Chung Hyeon | 25 | 6 | |
 Serbia | 31 | 7 | ||
| Steve Johnson | 33 | 8 | ||
| 34 | 9 | |||
 Georgia | 36 | 10 | ||
 Russian Federation | 37 | 11 | ||
 France | ||||
| Spain | 41 | 13 | ||
| 42 | 14 | |||
 Australia | 43 | 15 | ||
| 47 | 16 |
The following players received wildcards into the singles main draw:
The following players received entry from the qualifying draw:
The following players received entry as lucky losers:
Alexandr Dolgopolov → replaced by 
Guido Pella
Jared Donaldson → replaced by Franko Škugor Damir Džumhur → replaced by Dominik Köpfer David Goffin → replaced by Guido Andreozzi
Mikhail Kukushkin → replaced by Laslo Đere Feliciano López → replaced by 
Marcos Baghdatis Fernando Verdasco → replaced by Jaume Munar| Country | Player | Country | Player | Rank1 | Seed | |
|---|---|---|---|---|---|---|
 Poland | Łukasz Kubot |  Brazil | Marcelo Melo | 23 | 1 | |
| Jean-Julien Rojer |  Romania | Horia Tecău | 25 | 2 | ||
 Japan | Ben McLachlan | Jan-Lennard Struff | 53 | 3 | ||
| Julio Peralta | Argentina | Horacio Zeballos | 64 | 4 |
The following pairs received wildcards into the doubles main draw:
The following pair received entry as alternates:
See main article: 2018 Winston-Salem Open – Singles.
Daniil Medvedev def. Steve Johnson, 6–4, 6–4See main article: 2018 Winston-Salem Open – Doubles.
Horia Tecău def. James Cerretani / 
Leander Paes, 6–4, 6–2
