The Young Lions, making their first appearance in the competition for nine years, sit top of Group B after a solid victory at the Stade Leo-Lagrange thanks to goals from debutant Jordan Obita, midfielder Jake Forster-Caskey and substitute Jordan Cousins.
Gareth Southgate's U21 selection showed eight changes to the team that began Monday's 3-1 win over Wales U21s in European U21 Championship qualifying.
Nathan Redmond - the hat-trick hero in Swansea - was rested along with Jack Butland, Nathaniel Chalobah and Michael Keane. Carl Jenkinson, Tom Ince, Jesse Lingard and Danny Ings are not part of the squad in the south of France due to age restrictions.
Liam Moore, Luke Garbutt and James Ward-Prowse all kept their places in the side, with Jonathan Bond, Tyias Browning, Ben Gibson, Josh McEachran, Forster-Caskey, Solly March, Saido Berahino and Obita coming in.
Qatar lined up in a 4-4-1-1 formation and made it tough for England early on, but were eventually undone on the half-hour mark when Reading winger Obita hit a shot into the far corner after Ward-Prowse's initial shot was blocked.
McEachran and Berahino both went close before Forster-Caskey doubled England's lead nine minutes after the break, rifling home from Brighton team-mate March's lay-off.
Cousins replaced McEachran shortly afterwards and he rounded off a successful night for the U21s by netting from 25 yards with the last kick of the game when Qatar goalkeeper Yousef Hassan left his goal unguarded.
England U21s' next fixture is on Monday evening when they face Brazil, who beat South Korea 2-0 in their first fixture.
In Wednesday's Group A openers at the same venue, Portugal were 2-0 winners over Mexico before France saw off Chile 3-0.