Just three months on since Croatia beat England to reach the World Cup final for the first time, the sides meet again looking for their first points in the Nations League after both were defeated by Spain last month.
Sancho has been in stunning form for Borussia Dortmund to earn his first call-up to the senior side, but was left on the bench alongside fellow newcomers James Maddison and Mason Mount.
Ross Barkley made his first England appearance since May 2016 as Southgate looks set to ditch the 3-5-2 system that worked so well in Russia for a 4-3-3 with Raheem Sterling and Marcus Rashford flanking Harry Kane up front.
FIFA's world player of the year Luka Modric captains Croatia.
But the hosts weren't able to count on any support in their first home match since the World Cup with the game being played behind closed doors in Rijeka.
Croatia are completing a UEFA sanction to play two games behind closed doors after a swastika symbol was carved into the pitch during a Euro 2016 qualifier against Italy in June 2015.