Saka started at the Allianz Arena as Mikel Arteta named the strongest side available to him in the Gunners' toughest test of the season so far.
Those plans were ripped up inside the opening ten minutes of the match in what will be a significant concern for Arteta.
Saka had wriggled away from Alphonso Davies and got Arsenal on the attack, drifting into space and playing a pass out wide.
However, immediately after playing that pass under no real pressure, Saka went down clutching his left leg and signalled to the bench.
The winger had to be replaced and looked extremely uncomfortable as he hobbled off the pitch.
He stopped on the touchline to speak to Arteta and appeared to signal to his left quad, before continuing down the tunnel.
Injury scare: Bukayo Saka
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Eberechi Eze came on to replace Saka, as Madueke moved over to the right wing having started on the left.
Arsenal are already short in wide areas, with Christos Tzolis having been out of action since the international break with a hamstring injury.
If Saka does now face on the spell on the sidelines, it would leave Eze, Madueke and Max Dowman as the only fit wingers available to Arteta.
Arsenal have five matches in the next 17 days before the November international break, including a trip to Anfield to take on Liverpool in ten days' time.