The City forward found the net on 56 minutes at Wembley to edge a tense encounter against Croatia in Matchday One of Group D.
The 26-year-old slid Kalvin Phillips' through-ball home to bag his first senior tournament goal for his country, putting a precious three points on the board for the Three Lions.
All four City representatives – Kyle Walker, John Stones, Phil Foden and Sterling – were named in the starting XI to face the 2018 World Cup finalists, who had eliminated Gareth Southgate's side after extra-time in the semi-finals of the tournament in Russia three years ago.
Foden, who was named Player of the Tournament in 2017 as England won the Under-17 World Cup, earned his first senior start in a major international competition.
The PFA Young Player of the Year, sporting his new ‘Gazza-style’ haircut, almost enjoyed a dream start, curling an effort onto the post, having been played through by Sterling on the five-minute mark.
Competing on home soil and having never previously won their opening game at the Euros, the pressure was on England but the hosts started brightly with Sterling in particular seeing plenty of the ball in the early exchanges.
The forward, who has been awarded an MBE for services to Racial Equality in Sport in the Queen’s Birthday Honours list, looked to carve out opportunities on the left and fired a long-range half-volley off-target.
At the other end, Walker and Stones remained relatively untroubled - Ivan Perisic with a rare first-half half-chance for the visitors, blazing over the bar as the game settled before the break.
The deadlock was broken before the hour with two City men involved - Walker found Phillips, who spotted the run of Sterling and clipped the perfect pass into his path for the forward to finish first-time.
Harry Kane and Mason Mount then went close to doubling the advantage, while Ante Rebic and Marcelo Brozović skewed wide in search of an equaliser.
Foden was replaced with 20 minutes to go - moments before Sterling smashed over the bar.
The City forward's earlier strike would prove enough to claim victory though - a fitting triumph for the man who grew up in the shadow of England's iconic national stadium.
Sterling was replaced in injury time to deserved acclaim.
Matchday Two in Group D will see England face Scotland, who kick-off their tournament against the Czech Republic on Monday 14 June (14:00).
Southgate's side hosts the Scots on 18 June in a 20:00 kick-off, after Croatia and the Czech Republic lock horns at 17:00.
The Three Lions complete the group stage against the Czech Republic on 22 June - at 20:00 - while Scotland face Croatia at the same time.