Illinois (2-7, 0-6) lost its seventh game in a row.
The Buckeyes piled up 526 yards while holding the Illini to 160. It was the third game in a row the Buckeyes have scored at least 40 points, the first time Ohio State has done that since a four-game streak in 1995.
Smith completed 13-of-21 passes for a career-high 298 yards, and ran for 55 yards on seven carries. His scoring passes covered 41 and 3 yards to Santonio Holmes, and 73 yards to Ted Ginn Jr., who totaled 138 yards on four catches.
Over the past month, Smith has completed 65 percent of his passes for over 1,000 yards and 10 touchdowns.
Pittman totaled 96 yards on 22 carries, scoring on runs of 16 and 8 yards. He had not scored a touchdown all year until getting into the end zone twice a week ago in a 45-31 win at Minnesota.
Ginn, who had earlier fumbled a punt, returned the second-half kickoff 65 yards to help set up Smith's second scoring pass of the day to Holmes, a 3-yarder that gave the Buckeyes a 19-0 lead.
On the extra point, the snap went through the hands of holder A.J. Trapasso and Illinois strong safety Kevin Mitchell picked up the loose ball and ran 75 yards for a defensive conversion and the Illini's only points.
The Illini returned that gift on their next possession. On fourth-and-6 at the 24, punter Steve Weatherford faked the kick and rolled right. He was stopped short of the first down at the 29.
Four plays later, Smith faked a quick pitch to the right and then wheeled to flip the ball to Pittman who swooped around left end, took a hit, and then fought his way across the goal line to complete the 16-yard run. This time the Buckeyes did convert the point-after kick for a 26-2 lead.
To that point, Illinois quarterback Tim Brasic had completed 10-of-11 passes - but for only 16 yards.
Brasic finished 18-of-24 for 92 yards without an interception. He was sacked five times for losses totaling 31 yards, with linebacker A.J. Hawk picking up two of the sacks.
On Ohio State's next possession, Smith tossed a 50-yard pass to Ginn, who was all alone 5 yards clear of defender Sharriff Abdullah. Ginn waited on the pass, caught it and then easily coasted in to complete the 73-yard scoring play.
Ohio State led 13-0 at the half, scoring on field goals of 29 and 22 yards by Josh Huston before Smith tossed a pass into the left flat that Holmes turned into a 41-yard touchdown.
The Buckeyes were poised to add to their lead except for a late turnover. Illinois was forced to punt from deep in its end zone with just under two minutes left in the half, but Weatherford's kick was mishandled by Ginn and Cooper recovered at the Illinois 48.
Courtesy of the Illinois SID