The 33-year-old, who has endured a difficult run with injuries, limped off in the first half of La Rochelle's 26-15 loss to Bayonne.
It marked only his second outing since a calf injury ruled him out in early January.
"Season cut short. Thanks for all your messages," Skelton wrote on Instagram. "Always grateful, see you next year."
Skelton, who captained Australia at the 2023 Rugby World Cup, was also ruled out of two tests against Ireland and France in Wallabies' end-of-season tour last November, after sustaining an ankle injury while playing club rugby in France.
The latest setback is likely to see Skelton miss Australia's opening fixtures in the Nations Championship in July as well as the test against Japan on August 8.