Isner, the American number one, has not competed since he retired from his first-round match at the Australian Open on January 14 because of an ankle injury first suffered at the Hopman Cup earlier this month.
After Young has played Murray on the red clay surface at Petco Park, home of Major League Baseball's San Diego Padres, big-serving American Sam Querrey will take on Britain's James Ward in Friday's second singles match.
In Saturday's doubles, Bob and Mike Bryan are scheduled to meet Murray and Colin Fleming before the reverse singles are played on Sunday when Querrey comes up against Murray and Young faces Ward.
The United States have been crowned Davis Cup champion on 32 occasions and Britain will be bidding for their first victory over the Americans in the team competition since 1935.
World number six Murray will be spearheading the British challenge as he continues his return from back surgery, though he has expressed some concern over the playing surface at Petco Park.
"It's not really clay to be honest," Murray, who in July became the first British man to win Wimbledon for 77 years, told BBC Sport. "It's not like traditional European clay courts.
"It's a very, very slippy court. It's quick. It's a lot quicker than the surfaces we play on in Monte Carlo, Rome and Madrid, so it's been different.
"I'm hitting the ball fine, it's just getting used to the movement. All the players have been struggling with it because, like I say, it's very slippy."
Murray, after playing a Davis Cup tie against Croatia in mid-September, had surgery on his lower back. The Scot won his two singles matches in that tie to help Britain return to the World Group.
In his only two tournaments this year, Murray was beaten by Germany's Florian Mayer in three sets in the second round of Doha, then lost to Roger Federer after four sets in the Australian Open quarter-finals.
(Reporting by Mark Lamport-Stokes in Los Angeles; Editing by Gene Cherry)
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