Northwestern's Sam Simmons blows past Indiana's Randy Cate during the Wildcats' offensive explosion. (AP)

"You can just see it in his eyes. It's important to him. The good running backs want the ball and they want it every down. They don't think anybody can tackle them," Northwestern coach Randy Walker said.

The Hoosiers couldn't stop Anderson and now No. 22 Northwestern (5-1, 3-0) has won three straight conference games to go atop the Big Ten.

Anderson became the first Northwestern back to gain 200 yards in back-to-back games, surpassing 1,000 yards for a second straight season. He had touchdown runs of 1, 73, 15 and 2 yards as the Wildcats hit the 50-point mark for the first time since scoring 55 against Michigan in 1958.

Anderson was closing in on Mike Adamle's school record 316-yard performance set in 1969 but did not play the final 10 minutes.

"We don't break records in sixth game. If it's game 11, we might," Walker said when asked if he would have put Anderson back in the game.

"I try not to pay attention to stats," Anderson said, admitting he knew he had four touchdowns. "I caught it once that I had 247 yards, but as an offense we had to put Indiana out of the game. The yards are going to come."

The 5-foot-11, 202-pound Anderson has added speed this season and it's helped him beat linebackers to the outside after he takes the handoff from Kustok in the shotgun.

By spreading the field, Northwestern is, in essence, creating a game of 7-on-7.

"The whole focus of our offense is faster," Anderson said. "It puts the defensive backs and linebackers at a disadvantage. Instead of me reacting to them, they're reacting to me."

Anderson's rushing total is the third best this season. TCU's LaDainian Tomlinson had 294 on Saturday against Hawaii, and Wisconsin's Michael Bennett gained 293 against Northwestern in the Wildcats' 47-44 overtime victory two weeks ago.

Northwestern couldn't completely stop elusive quarterback Antwaan Randle El, but the Wildcats certainly slowed him and an offense that was averaging 39 points a game. Using backups, the Hoosiers (2-3, 1-1) scored two late touchdowns after the outcome was decided.

"It's hard to play catchup, said Randle El, who ran for 80 yards and passed for 165. "We're not in a position to do that. We put ourselves in a really bad situation."

Kustok threw touchdowns passes of 23 yards to Sam Simmons in the first quarter and a 50-yarder to Teddy Johnson in the third. Four minutes later, Anderson broke off his 15-yard scoring run to give the Wildcats a 38-14 lead.

Simmons, also the Wildcats' kick returner, had to leave the game in the second quarter when he aggravated a stress fracture in his back.

Randle El had a 50-yard run to set up De'Wayne Hogan's 9-yard run in the second quarter and tossed a 4-yard touchdown pass to Kris Dielman early in the fourth, but spent most of his day avoiding the Wildcats' rush.

Anderson, who ran for 219 yards against Michigan State a week ago, tightroped the sideline on his 73-yard scoring run that put the Wildcats ahead 21-7 in the second quarter, en route to a 24-14 halftime lead.

Northwestern used two Indiana mistakes for its first two touchdowns.

Indiana punter Andy Payne was ruled to have touched his knee to the ground after he picked up a low snap. That gave Northwestern the ball at the Indiana 43 and after two 8-yard runs by Anderson, Kustok hit Simmons on a 23-yard touchdown pass.

Randle El then completed a pass to Versie Gaddis near the sideline on the Hoosiers' next scrimmage play but he fumbled after a hit by Harold Blackmon and Rashidi Wheeler recovered for the Wildcats.

Northwestern then quickly moved 73 yards with Anderson breaking off runs of 13 and 12 yards after a personal foul penalty on Indiana. Anderson's 1-yard run gave the Wildcats a 14-0 lead after one quarter.