The Illini (2-1) were missing a handful of starters who were injured, including quarterback Nathan Scheelhaase, who has missed two games with a sprained ankle. O'Toole got the start and connected with Lankford twice in the first quarter for short touchdowns that gave the Illini a 13-0 lead, all they would need.
Illinois held Charleston Southern (0-3) to 125 yards of offense. It was the first game against a Big Ten team for the FCS Buccaneers.
Even with O'Toole's big day, the most important play of the game for the Illini might have come from freshman running back Dami Ayoola.
Illinois jumped ahead early 13-0 on a pair of 4-yard first-quarter touchdown passes from O'Toole to Lankford, but stalled offensively as the second quarter dragged on.
Facing a fourth-and-1 at the Charleston Southern 28, the 5-10, 205-pound Ayoola got the ball and quickly pushed into the center of the Buccaneer line for the first down. But no one brought him down, and Ayoola popped out of the pile stumbling but still on his feet.
He straightened himself out and sprinted to the end zone for a touchdown.
With the extra point Illinois had a 20-0 lead that, even with 2:06 left to play in the first half, looked comfortable. The Buccaneers have yet to score more than 14 points in a game this season.
Ayoola finished with eight carries for a game-high 55 yards. He played in place of starting back Josh Ferguson, who missed the game with a concussion.
Even with Scheelhaase out, Illinois' defense came into Saturday's game knowing it was the primary problem in last week's loss at Arizona State. Players said they had trouble reading the play calls from the sideline, and the Sun Devils built a 28-0 halftime edge before going on to win 45-14.
But Charleston Southern's option offense seldom troubled the Illini defense Saturday.
The more limited Buccaneers managed just 125 yards of offense against the Illini. A rotating cast of quarterbacks were a combined 5 of 14 for 29 yards, including an early interception that set up Illinois' first touchdown.
Charleston Southern really threatened only once.
Illinois led 13-0 midway through the second quarter when Buccaneers backup quarterback Briar Van Brunt kept the ball on the option and broke away from the Illinois defense for a 54-yard gain. V'Angelo Bentley and Justin Green caught him from behind at the Illinois 38.
But the Buccaneers' first trip into Illini territory didn't last long. Two plays that went nowhere and a penalty for having 12 players on the field left Charleston Southern with a third-and-15 at the Illini 43. Quarterback Derek Hatcher's wobbly floater was too high for Corvaughn Archie to pull down, and the Buccaneers were forced to punt.
Illinois went into the game missing three starters on each side of the ball.