According to the report, Jackson will be out four to six weeks with a broken left hand. Lynch will miss three to four weeks with a sprained ankle.
The Bills have three preseason games left. The regular-season opener is four weeks away on Sept. 12 against the Miami Dolphins in Buffalo.
Both backs were hurt on the opening drive of Friday night's lopsided preseason loss to the Washington Redskins.
Rookie running back C.J. Spiller will likely get the bulk of the workload for the remainder of the preseason. He was the ninth overall pick in April's draft, but he doesn't provide the same substance as Jackson or Lynch.
Spiller, a dominant player in college, was hardly a workhorse at Clemson. He averaged only 15.4 carries a game his senior year.
Tim Graham covers the AFC East for ESPN.com.