Sarah Young, a personal lifestyle company owner from London, was knocked overboard by a wave in the Pacific Ocean.
She was one of the crew on the IchorCoal boat (CV21), sailing from Qingdao in China to Seattle in the US.
Skipper Darren Ladd said she was tidying the cockpit in strong winds when she was swept away by a wave.
She was not tethered to the yacht at the time, and the rescue was hampered by bad weather.
Her body was recovered, but she could not be resuscitated.
"The cause of death is yet to be confirmed but is suspected as drowning or exposure," race organisers said in a statement. All other crew are reported safe and well and the team are working with race officials to evaluate the options on diversion or continuing to Seattle."
Her death comes six months after Andrew Ashman, 49, from Kent, was killed on the same vessel after being knocked unconscious while sailing off the Portuguese coast.
The two Britons are the only fatalities in the 20-year history of the race.
Ms Young was knocked overboard in the mid-north Pacific at around 1.44pm UK time on Friday.
Founder Sir Robin Knox-Johnston, the first person to sail solo non-stop around the world, said he was "deeply saddened" by her death.
"She was a very popular and integral member of the Clipper Race family and knew our boats well, having sailed with us since London last summer," he said. "The safety of our crew has always been and continues to be our main priority and we shall investigate the incident immediately in full cooperation with the authorities."
A race spokeswoman said: "Sarah was the owner of a personal lifestyle company providing services for private high net worth individuals. A keen adventurer, the Clipper Race had been an ambition of hers for some years, and she said celebrating her 40th birthday just before setting sail from London was the perfect way to start her adventure."
The race is around 40,000 miles long and starts and ends in London. It takes almost a year to complete.