Murray has traditionally struggled in the Californian desert – reaching just one final, in 2009 – and was at a loss to explain his latest ignominy.
The Scot gifted four breaks of serve to Pospisil who scored his biggest career win with a 6-4, 7-6(5) triumph.
“I don’t know exactly why it is, because in practice I normally play pretty well,” said Murray after the loss.
“Some years I’ve played well. Some years it just hasn’t quite happened for me.”
Indeed, the three-time Grand Slam champion admitted after his departure in Indian Wells last year to the hands of Federico Delbonis that the conditions in the desert do not complement his game.
However, Murray entered the tournament having reigned supreme at the Dubai Duty Free Championships, where the court is of similar condition to Indian Wells.
The Canadian was forced to come from a set behind against Lu Yen-Hsun in round one after battling through qualifying and Murray says that his opponent’s discipline proved key in the end.
“He’s always played that way, maybe he was doing it better this evening,” he added.
“He was maybe a bit more solid from the back, a bit more consistent from the back of the court.”
Pospisil hailed it as the “biggest win” of his career after he wrestled with injuries in 2016 and saw his ranking plummet outside the top 100.
Elsewhere, the mercurial Fabio Fognini stunned the Frenchman Jo-Wilfried Tsonga, winner of two ATP titles in 2017, with a three-set victory.