His withdrawal comes after second seed Joao Fonseca of Brazil also pulled out.
"Unfortunately, I have to withdraw from Eastbourne this year," the American said on X. "I waited up until after the match warmup to make the decision today because I really did want to play.
"This is never an easy decision for me, especially when it involves a tournament that means so much to me. While I know it's the right call, it doesn't make it any less disappointing."
The 28-year-old world number seven has won the Wimbledon warm-up event four times in total and will be expected to make a deep run at the All England Club.
He has shown strong form on grass so far this year, reaching the final in Halle and Stuttgart.