Muller struck 12 minutes after his half-time introduction before Lewandowski doubled the lead and Sebastian Rudy added a third as coach Jupp Heynckes started a weakened team.
"All in all, we played excellent football," beamed Heynckes. "The team is in top form, regardless of who plays and in what position. When you have a Champions League game on the horizon, it's important to win league games like this."
With an eye on Wednesday's blockbuster Champions League semi-final first leg at home to Real, Heynckes left out several regulars while handing 18-year-old centre-back Lars Lukas Mai his Bundesliga debut.
Both sides had their chances in a goalless first half before Bayern pulled away.
After Muller replaced Arjen Robben, the Germany international struck on 57 minutes when his first-time shot from a Juan Bernat cross deflected off Salif Sane and past goalkeeper Philipp Tschauner.
Bayern's top scorer Lewandowski added a second just six minutes after coming on himself for his 38th time this season in all competitions.
Defensive midfielder Rudy capped the win a minute from time to leave Bayern 23 points clear of second-placed Schalke, who are at bottom side Cologne on Sunday.
Later Jadon Sancho and Marco Reus inspired Borussia Dortmund to a 4-0 romp at home to Bayer Leverkusen.
Even with striker Michy Batshuayi sidelined by an ankle, the pair shone in front of goal.
Sancho, 28, a former Manchester City winger, leapt for joy after becoming the youngest Englishman to score in the Bundesliga when he hit the bottom corner with 13 minutes gone.
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