The former Manchester United winger is awaiting trial after being charged with controlling and coercive behaviour and assault against his ex-girlfriend and her sister.
The trial at Manchester Crown Court had been due to start on Jan 24, but has been delayed until Aug 8, a factor that lead to the 48-year-old deciding to step down now.
"After much consideration, I am standing down from my position as manager of the Wales men's national team with immediate effect," Giggs said in a statement.
"It has been an honour and a privilege to manage my country, but it is only right that the Wales FA, the coaching staff and the players prepare for the (World Cup) tournament with certainty, clarification and without speculation around the position of their head coach.
"Through nobody's fault the case has been delayed. I do not want the country's preparations for the World Cup to be affected, destabilised or jeopardised in any way by the continued interest around this case."
Giggs temporarily stepped down as Wales coach in November 2020, with Robert Page guiding the nation to their first World Cup finals since 1958 earlier this month after a play-off victory over Ukraine.
The Football Association of Wales (FAW) confirmed they accepted Giggs' resignation.
"The FAW places on record its gratitude to Ryan Giggs for his tenure as manager of the Cymru Men's National Team and appreciates the decision he has taken, which is in the best interests of Welsh football," a statement read on Monday.
Giggs has pleaded not guilty to all charges and remains on bail.