The Arsenal youngster, widely regarded as one of the brightest talents of his generation, had travelled with the senior squad but was left out of the official matchday selection in order to comply with UEFA's squad limit.
England can register only 23 players per fixture, meaning Thomas Tuchel must rotate his options from game to game.
Despite the setback, Lewis-Skelly remains highly rated within the England camp and is expected to play a role in the qualifying campaign. The decision is believed to be tactical rather than a reflection on the left-back's recent form at club level.
The move follows a similar decision in England's last outing, when Bayer Leverkusen defender Jarell Quansah was the player to miss out against Andorra.
With competition for places at an all-time high, Tuchel is keen to manage his squad carefully as England push for early qualification.