I researched this exact question for
a Sporcle quiz, and in the United States the winner for city population drop is Highland Park, Michigan.
A cutoff of 50,000 at the peak qualifies a surprisingly large number of Rust Belt cities.
Updating to 2015 estimates:
City..........Peak..........2015........Percentage Drop
Highland Park, MI.............52,959..........10,949.......79.3%
Johnstown, PA................19,966...........67,327......70.3%
East St. Louis, IL.............82,366...........26,790......67.5%
McKeesport, PA...............55,355...........19,453......64.9%
Detroit, MI.....................1,849,568.......677,116.....63.4%
St. Louis, MO..................856,796.........315,685.....63.2%
Youngstown, OH..............170,002.........64,628.......62.0%
Hamtramck, MI................56,268...........22,002.......60.9%
Cleveland, OH.................914,808.........388,072......57.6%
Gary, IN.........................178,320.........77,156.......56.7%
Buffalo, NY.....................580,132.........258,071......55.5%
Wheeling, WV..................61,659...........27,648......55.2%
Pittsburgh, PA.................676,806.........304,391.....55.0%
Wilkes-Barre, PA..............86,626..........40,780.......52.9%
Niagara Falls, NY..............102,394.........48,916.......52.2%
East Chicago, IN..............57,669...........28,699......50.2%
Flint, MI.........................196,940.........98,310.......50.1%
Saginaw, MI....................98,265..........49,347.......49.8%