There will be both short- and long-term closures, beginning at 6 p.m. Friday, through 9 a.m. Saturday, the Chicago Department of Transportation said.
The closures will primarily be on LaSalle Street between Jackson Boulevard and Washington Street.
Motorists should expect delays and limited street parking.
Several downtown streets also closed last weekend, as filmmakers again turned parts of downtown Chicago into Gotham City.
Several downtown Chicago streets close temporarily for 'The Batman' filming this weekend: CDOT
Chicago Traffic: Click Here
The film stars Robert Pattinson, Zoe Kravitz and several other big names.
"It means a lot, another Batman movie here in Chicago," said Orlando Cadenas, who posted up just outside the filming perimeter early Saturday morning. "It's the best."
Last week's street closures were primarily near the Thompson Center and the intersection of Michigan Avenue and Balbo Drive, officials said.
Vehicles could be seen whizzing through the area, and "Gotham City" police cars were parked along the curbs, as well.
The video in the player above is from an earlier report.