The 33-year-old is named the Hoops new boss after a successful spell as interim manager at Wealdstone last season.
Cox, the former Hampton, Welling and Barnet player. helped the Stones defy the odds to secure survival in the National League but that fantastic late surge wasn’t enough to earn the job full time.
Their loss is Oxford’s gain and he has replaced Ross Jenkins, who was named Luke Garrard’s successor at Boreham Wood last month.
Cox is thrilled to accept the position as he gears up for a challenging season in the Vanarama National League North.
“I’m delighted to get the deal over the line,” he said. “My first impressions of this football club are tremendous. There’s some really good people around the place and after years of playing against Oxford, I know how well run the club is.
“I’m really looking forward to getting going, starting the season and trying to take this football club to where it deserves and needs to be.”
Oxford City owner Justin Merritt said: “We’re really pleased to welcome Sam to Oxford City as our new men’s first team manager.
“We were extremely impressed with the quality of candidates throughout an in-depth recruitment process, but Sam was the stand-out candidate. He is a fantastic fit for what we are trying to achieve, with a strong coaching CV with the likes of Tottenham and Wealdstone.
“Sam also brings international experience with his role as assistant manager of Guyana and will build upon the possession-based style of football we have developed over as a club over recent seasons.”