Friedel's place in the Spurs team has been under threat ever since Villas-Boas signed France skipper Lloris from Lyon for £8million on transfer deadline day.
The Spurs boss chose 41-year-old Friedel for the following four games, using Lloris only in the Europa League.
But on Sunday he decided to drop Friedel, bringing to an end a hugely impressive run for the American that began in 2004 while he was at Blackburn.
Friedel has been in imperious form for Tottenham this term, with his stand-out performance coming against Norwich last month when he almost single-handedly stopped the Londoners from slipping to defeat.
The American, who has also played for Liverpool, Galatasaray and Sunday's opponents Villa, may have conceded two at Old Trafford last week, but neither were disastrous mistakes.
Villas-Boas must have decided that now is the time to see if Lloris has what it takes to cut it in the Premier League.
Lloris' introduction for Friedel was the only change to Villas-Boas' side as they looked to register their fourth straight league win.
Source: PA
Source: PA