Citigroup Inc. is preparing for a wave of job cuts as Chief Executive Officer Jane Fraser launches the biggest restructuring of the Wall Street giant in two decades, part of her effort to reverse a years-long slump in the stock price.

The company will now operate five main businesses and eliminate the three regional chiefs who oversee operations in about 160 countries around the world, according to a statement Wednesday. At least four of Fraser’s senior deputies got new roles in the shakeup, and the firm is looking for a head of banking, which includes oversight of the investment-banking unit. …