Matthew Prior was named as wicketkeeper in the 12-man squad announced by the England and Wales Cricket Board (ECB) on Sunday.
Peter Moores will be in charge of the team for the first time, having taken over as coach from Duncan Fletcher, who resigned last month after England's poor showing at the World Cup in the Caribbean.
Vaughan is recovering from a broken finger and might have been fit by Thursday, but chairman of selectors David Graveney said his and his co-selectors did not want to take any risks.
"There was a very slim chance of him playing (and) we didn't want to go down the route of injections," Graveney told BBC Radio Five Live.
Graveney told the ECB Website (www.ecb.co.uk): "Michael Vaughan has made progress with his recovery from injury but his chances of being fully fit for this Test match are extremely doubtful and we feel the best course of action is to avoid any uncertainty and for Andrew Strauss to deputise for him.
"Michael will continue his rehabilitation with the squad at Lord's next week and we will reassess his fitness when we sit down to pick the side for (the second Test at) Headingley."
Strauss has captained England before, leading them to a 3-0 Test series win over Pakistan last summer.
STRAUSS PREFERRED
The choice of stand-in captain was between Strauss and all-rounder
Flintoff was sacked as England's World Cup vice-captain for a late-night drinking session in the Caribbean but Graveney said this had had no bearing on the selectors' decision.
"Our view is that the team's best interests will be served if Andrew Strauss leads the team as this will allow Andrew Flintoff to concentrate on his batting and bowling," Graveney told ecb.co.uk.
Prior is preferred to World Cup keeper Paul Nixon and will make his Test debut in the first match of the four-Test series.
"Matt averages nearly 40 with the bat in first-class cricket and this was an important factor in reaching our decision," Graveney said.
Talismanic middle order batsman Kevin Pietersen was included despite slight doubts over his fitness. He suffered a calf strain playing for Hampshire last week.
"We are very optimistic that Kevin Pietersen will be fit and we do not have any other injury concerns leading into this Test match," Graveney said.
Batsman Owais Shah has been recalled, most likely as Vaughan's numerical replacement, although Graveney said: "Owais Shah has been included in the squad to provide cover for Kevin but also to give us the option of playing a stronger batting line-up if required."
Team: Andrew Strauss (captain), Ian Bell, Paul Collingwood, Alastair Cook, Andrew Flintoff, Steve Harmison, Matthew Hoggard, Monty Panesar, Kevin Pietersen, Liam Plunkett, Matt Prior, Owais Shah.
