Friedel, 41, has not missed a top-flight game since the end of the 2003-04 season, a remarkable sequence of 310 successive matches for Spurs and former clubs Villa and Blackburn Rovers.
Lloris joined Spurs from Olympique Lyon on the last day of the transfer window in August for a transfer fee of £12 million.
That put Friedel's place in jeopardy, but the Spurs boss chose 41-year-old Friedel for the following four games, using Lloris only in the Europa League.
But 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 had 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 benching of the American, who has featured in three World Cup squads and also played for Liverpool, Galatasaray and Villa, was the big talking point before kick-off.
Yet the choice of the goalkeeper proved unimportant: Lloris had little to do as his team dominated proceedings and could have won even more easily but for squandering a hatful of chances.