Also, receiver Harry Douglas will miss his second straight game with a foot injury.
Blalock's injury ends a streak of 102 consecutive starts, the longest on the team. It also leaves the Falcons (2-2) with huge questions up front as they face the surging Giants (2-2).
Atlanta lost center Joe Hawley and right tackle Lamar Holmes to season-ending injuries in a loss at Minnesota last Sunday. Peter Konz will start at center, while Gabe Carimi is working in Holmes' spot. Blalock will likely be replaced by former practice squad player Harland Gunn.
"We've been rotating the guys through and working on different combinations," Smith said on Friday. "It's very important for us to have a plan A, B and C, as we found out last week. I still believe we'll be able to move the ball efficiently whether we're running it or throwing it."
Shembo has a sore knee and Ishmael a sore ankle. Ishmael has stepped in for William Moore, who's out the next eight weeks with a shoulder injury.
Jones, a 2012 Pro Bowl selection who missed most of last year with a broken right foot, leads the NFL with 11 catches of 20 or more yards.
Hester, the league's career leader in touchdown returns with 20, is the No. 3 receiver with Douglas out.