Kane, on five goals so far in this World Cup, and four-goal Lukaku currently lead the top scorer standings alongside Cristiano Ronaldo.
The Portugal star has played one game more than the Premier League pair, but they may not get a chance to hit the score-sheet again in this first round as both England and Belgium rotate their line-ups.
Spurs' striker comes out for Leicester's Jamie Vardy, while Michy Batshuayi starts up front for the Red Devils.
Dele Alli, Raheem Sterling, Kyle Walker, Jordan Henderson and Jesse Lingard also make way in a much-changed team.
Belgium boss Roberto Martinez, meanwhile, makes no less than nine changes to the team that defeated Tunisia to seal qualification.
Only goalkeeper Thibaut Courtois and defender Dedryck Boyata keep their places, with the likes of Eden Hazard, Kevin De Bruyne and Dries Mertens all joining Lukaku on the bench.
England: Pickford, Alexander-Arnold, Jones, Stones, Cahill, Rose, Dier, Delph, Loftus-Cheek, Rashford, Vardy.
Belgium: Courtois, Dendoncker, Boyata, Vermaelen, Chadli, Dembélé, Fellaini, Tielemans, T. Hazard, Januzaj, Batshuayi.