The former Tottenham Hotspur and England striker replaces Neal Ardley at the Laithwaite Community Stadium after a thorough recruitment process.
Although Defoe has gained coaching experience through an interim spell at Rangers FC and within the Tottenham academy system, this marks his first permanent managerial appointment.
"Woking is a historic club with huge potential, and I’m thrilled to be part of this exciting project. I can’t wait to get started," Defoe said.
Woking chose the football great following an extensive interview process, with club chairman Todd Johnson highlighting his modern football philosophy and clear long-term vision as key factors in the decision.
The former Premier League forward has expressed excitement about beginning his managerial journey in full control of a team.