Wales meet South Africa in less than two months and new coach Warren Gatland faces an anxious wait as influential flanker Williams undergoes a scan later today.
Williams, 33, said: "The doctors aren't speculating but it looks like ligament damage. I hope I won't be out for too long and back in a few weeks - it just depends how severe it is.
"My foot got stuck under a couple of people in the tackle and rolled the ankle. I knew it was pretty sore when I did it. I tried to carry on but I couldn't put any weight on it.
"The doctors want to wait for the swelling to go down and see how it reacts before I have the scan."
Wales face the world champions in Cardiff on November 8 before clashes with Canada, New Zealand and Australia.
Gatland's other options at openside flanker include fit-again Robin Sowden-Taylor, Jonathan Thomas or Gavin Thomas.
It's Williams' second injury blow in just four months after he missed the summer tour to South Africa with knee ligament damage back in May.
British and Irish Lion Williams retired from international rugby after the 2007 World Cup before Gatland persuaded him to change his mind for last season's Six Nations.
The 81-cap flanker was an instrumental figure in the dragons' Grand Slam triumph and scored the winning try in the decider against France at the Millennium Stadium.
Cardiff Blues coach Dai Young said: "Hopefully it's not too bad not only for our sake but Wales' too.
"You don't see Martyn come off the field unless he's taken a bang."