Born in Bilbao to Ghanaian parents, Williams has made one appearance for La Roja at senior international level but in a friendly, coming on as a substitute against Bosnia and Herzegovina in 2016.
Also part of Spain's run to the Under-21 Euro 2017 final, Williams' ability to switch allegiance falls under FIFA's eligibility rules change of 2003, when Tim Cahill opted to play for Australia after representing Western Samoa at junior level.
Posting on social media, the 28-year-old striker believes it is an opportunity to cultivate a deeper connection to his origins.
"Every step we take forward has its own meaning - a glance into the future which leaves a trace itself," he said. "A legacy. My parents have raised me with values based on humility, respect and love.
"That's why I feel the moment has come for me to find my origins within myself and with Africa and Ghana which means so much to me and my family."
At club level, Williams holds the LaLiga record for consecutive appearances at 233 games, after breaking the previous mark of 202 in October.
Ghana Football Association president Kurt Okraku also tweeted Tariq Lamptey, Stephan Ambrosius, Patric Pfeiffer and Ransford Yeboah are all set to confirm their allegiance to the Black Stars.
All five diaspora members could bolster Ghana's prospects at this year's World Cup, where they have been grouped with Portugal, Uruguay and South Korea.