Stories of a split mounted after technology new website AllThingsD first reported that the 40-year-old and his wife, an entrepreneur behind genetic testing firm 23andMe, are living apart.
Brin, who heads a special Google unit devoted to unusual projects such as self-driving cars and internet-linked eyewear, has been linked with a 26-year-old member of the Google Glass team, Amanda Rosenberg.
California-based Google declined to comment on the Brin breakup other than to confirm an amicable parting had taken place.
Brin and Wojcicki have a son and a daughter.
They reportedly met through Wojcicki’s sister, who rented a Silicon Valley garage to the Google co-founders Brin and Larry Page.
Brin and Page used the garage as a base of operations after moving from a dormitory at Stanford University where they were students.
Brin has a personal fortune of $22 billion and it is believed the couple signed a pre-nuptial agreement before they wedded.
Ms Rosenberg attended the University of Leeds before joining Google in London in 2008 after graduating. She later went on to move to San Francisco and has been heavily involved in the marketing of Google Glass.
Ms Rosenberg was named as Mr Brin’s new partner by Valleywag, a Silicon Valley news blog and was previously romantically linked to Hugo Barra, another senior executive at Google, who has since departed the company.
Google has invested in 23andMe, which Anne Wojcicki founded with Linda Avey. It offers genotyping services to individuals interested in learning inherited health risks.
Several years ago, Brin made his blogging debut by writing of his mother being diagnosed with Parkinson’s disease and how testing by 23andMe showed he has a gene mutation that “markedly” increases his chances of getting the illness.
Brin told of working with The Parkinson’s Institute and the Michael J Fox Foundation to combat the disease.
Brin and Anne Wojcicki have been involved in an array of business and philanthropic endeavours, including an eponymous foundation to which they have contributed heavily.