Lewandowski suffered a knee injury after scoring two goals in Poland’s 3-0 win over Andorra over the weekend.
The 32-year-old has been ruled out of action for up to a month and in addition to the game against the Three Lions, Lewandowski will also miss both legs of Bayern Munich’s UEFA Champions League quarterfinal clashes with French champions Paris Saint Germain.
England have begun their road to Qatar with two wins and two clean sheets but Poland are only two points behind their next opponents.
Southgate believes Poland remain a strong side even in the absence of their record goalscorer and has urged his England players to brace themselves for a tough ride.
"From our perspective, you're going to have players who are hungry to fill that opportunity," Southgate said at a pre-match news conference on Tuesday.
"They're a good side with some good players. They will all fight for the cause and they're a good football team. They've got high motivation.
"We've got to keep improving. We've shown a good level and we've got to keep stepping up.
"I understand the question, but I think Poland have excellent players. We would be naive to think they are less of a threat.
"If we think of taking our foot off the gas, we'll get hurt. Of course, the public want to see the star names, but a team isn't about one player."
