Best sidelined for up to six weeks
"Leon Best will have a scan on Tuesday on his injured left knee and is likely to be out for a number of weeks," the club said on their website.
Local media reported Newcastle manager Alan Pardew as saying the player would be out for up to six weeks.
The 25-year-old Ireland striker was forced out of Sunday's 2-1 home win after 14 minutes and was replaced by new signing Papiss Cisse who scored a spectacular winning goal on his debut.
There was better news for Newcastle midfielder Ryan Taylor who was carried off on a stretcher in the same game after a collision with Villa defender Stephen Warnock in the build-up to the hosts' opening goal.
"Fortunately, Ryan Taylor did not sustain a fracture to his lower right leg which was X-rayed on Sunday afternoon," the club said.
"His injury is limited to soft tissue damage for which he is now receiving treatment from the club's medical team."
Sunday's win moved Newcastle up to fifth in the Premier League, one point behind Chelsea in fourth.