With a chill wind blowing and drizzle falling on the Simonne-Mathieu arena, the 40-year-old Williams began strongly but got bogged down in a baseline battle on a slow surface.
The American has now fallen in the opening round at the French Open for the past three years.
Williams led 3-1 and 4-2 in the first set against the 26-year-old who is playing under a special ranking after undergoing knee surgery.
But she lost a series of lengthy games as a first set lasting 68 minutes slipped away.
Unable to hold her once mighty serve, Williams, the oldest player in the draw, fell 4-1 down in the second set.
This came as Schmiedlova moved within sight of snapping a streak of 12 successive Grand Slam first round defeats since 2016.
Williams, who played in black leggings and a bodywarmer, finally held serve.
That was after being broken six times in a row to close to 3-4 in the second as Schmiedlova began to look a little nervy.
But the Slovak edged 5-3 in front.
Seven-times Grand Slam champion Williams fought ferociously until the end, saving two match points on serve.
But Schmiedlova showed great composure to serve it out, sealing victory with a forehand down the line.
Williams, playing her 87th Grand Slam and now ranked 76th in the world, also lost in the opening round at the U.S Open.
It was the first time she had fallen at the first hurdle at her home Slam in 22 appearances.(Reuters/NAN)
•PHOTO: Venus Williams

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