Venus Williams loses to Swiss teen on return from five-month injury layoff
With sister Serena, who retired last year, watching on in the crowd, Williams started brightly but lost the closely fought second in the tiebreak before fading in the decider on Tuesday.
The former world number one, a five-times winner at Wimbledon, lost 3-6 7-6 (6-3) 6-2 to 17-year-old Naef in two hours and 18 minutes.
"I cannot believe I had the chance to play against Venus," Naef said after her first win on the WTA Tour. "She's an amazing player and really a role model for anyone."
Williams, who was handed a wildcard for the tournament, had been sidelined since January after sustaining a hamstring injury in Auckland that forced her to withdraw from the Australian Open.
She won her last major singles title at the grass-court Grand Slam in 2008. This year's Wimbledon tournament begins on July 3.