The job cuts will be partly offset by jobs that the company expects to add this year.
American Express said the jobs eliminated will span employee seniority levels and divisions worldwide, but will primarily involve positions that do not directly generate revenue for the company.
All told, the company anticipates that staffing levels will end up between 4 and 6 percent lower this year than in 2012. The company currently has 63,500 employees.
"Against the backdrop of an uneven economic recovery, these restructuring initiatives are designed to make American Express more nimble, more efficient and more effective in using our resources to drive growth," said CEO Kenneth Chenault.
Shares slipped 29 cents to $60.50 in after-hours trading. They ended regular trading up 53 cents at $60.79.
American Express said it will book an after-tax charge of $287 million due to the restructuring. It's also recording $212 million in expenses related to reward points for its cardholders and roughly $95 million in customer reimbursements and other costs.
The combined charges will reduce American Express' fourth-quarter net income by 46 percent from a year earlier.
The company projects net income of $637 million, or 56 cents per share, compared with net income of $1.2 billion, or $1.01 per share, in the same quarter of 2011.
Excluding one-time items, fourth-quarter 2012 earnings amount to $1.2 billion, or $1.09 per share, ahead of analysts' consensus forecast of $1.06 per share, according to FactSet.
Revenue rose 5 percent to $8.1 billion. Analysts expected $8.01 billion.
The company is scheduled to report full results next Thursday.
Overall American Express has done well after the recession, as upscale shoppers have spent freely. That's because Amex cardholders are in general about a third more affluent than other credit card holders.
Through the first nine months of 2012, revenue grew 5 percent, while net income rose 3 percent.
Spending by cardholders jumped 8 percent in the fourth quarter, despite some softening early in the period due to Superstorm Sandy, the company said.
Chenault noted that, since the recession, American Express has been consistently gaining market share.
Despite that success, he said the company must embrace new technologies, become more efficient and position itself to invest in growth opportunities in a marketplace that's increasingly becoming defined by consumers' use of the Internet and mobile technology.
To that end, American Express' restructuring plan calls for overhauling its travel business to cut costs and invest in ways to cater to a growing volume of customers turning to online and automated tools to make their travel arrangements.
"One outcome of this ongoing shift to online is that we can serve a growing customer base with lower staffing levels," Chenault said during a call with analysts.
The company also will reconfigure its cardholder servicing and collections operations to focus more on online and mobile, rather than telephone and mail.
"The overall restructuring program will put us in a better position as we seek to deliver strong results for shareholders and to maintain marketing and promotion investments at about 9 percent of revenues," Chenault said.