The billionaire Swiss businessman rescued the club from the brink of extinction in July 2009 when he completed an estimated £13m takeover.
No cause of death was given.
Liebherr was a member of wealthy family who specialise in construction machinery, although he operates independently through his own group of companies, the Mali Group.
“To say he will be missed is an unmistakeable understatement,” the club said in a statement.
Southampton FC assured fans that Liebherr’s passing will not affect its future. It said: “The club will ensure that Markus’ wishes are carried out in full. The Saints were Markus’ constant preoccupation. He certainly didn’t like losing.”