The Athletic Bilbao captain made the announcement in a statement on Instagram, accompanied by a series of images of him wearing the Black Stars shirt, bringing an end to a four-year international spell that began in 2022.
"I feel that the time has come to end my time with the Ghana national team," the statement began. "I leave happy, proud and with the peace of mind of knowing that I gave everything every time I wore this shirt."
Williams had made his senior debut for Spain in 2016, but in July 2022 announced his decision to switch allegiance and represent the country of his family's roots.
He received his first call-up that September for friendlies against Brazil and Nicaragua, making his debut on 23 September at the Stade Oceane in Le Havre in a 3-0 defeat, coming on for Kamaldeen Sulemana at half-time. He went on to earn 28 caps and score twice for Ghana, representing the country at the 2022 and 2026 World Cups as well as the 2023 Africa Cup of Nations.
"Ghana has given me much more than football. It has allowed me to come back home, feel even closer to my roots and experience the enormous pride of representing my country and wearing this flag on my chest," Williams continued.
"Thank you from the bottom of my heart to everyone who has been part of this journey and for all the affection you have always shown me. Ghana will always be a part of me. I will continue supporting the national team. As one of you, wherever I am."
Williams, 32, will now focus fully on his club career at Athletic Club, where he is currently being used as a central striker by new head coach Edin Terzic, who succeeded Ernesto Valverde over the summer.
With his son Niko among his priorities, Williams, a player who relies heavily on his physical attributes, wants to remain fully focused on the closing stages of his playing career at San Mames and continue supporting his brother Nico Williams, whose own career with the Spain national team continues to flourish.