ANN ARBOR, Mich. -- With one-third of the regular season finished, No. 4 Michigan has done exactly what many expected it do: Defeat inferior opponents.

The latest victim was Penn State, which was sent back to Happy Valley feeling sad after Michigan dominated in just about every phase of the game to earn a 49-10 over the Nittany Lions in the Big 10 opener for both teams at Michigan Stadium on Saturday.

Next up for Michigan (4-0) is a showdown with unbeaten Wisconsin next Saturday at Michigan Stadium in what assuredly will be a matchup of top-10 teams and provide Michigan with a measuring stick it hasn't gotten this season.

Michigan rushed for a season-high 326 yards and amassing 515 yards of total offense.

Senior De'Veon Smith ran for 112 yards and a touchdown on 12 carries and four other Michigan running backs ran for touchdowns.

"I was really impressed with the running backs," Michigan coach Jim Harbaugh said. "All of them contributed big plays. I thought our line blocked well and it was a job well done by the running game."

Michigan controlled the game just as much when Penn State had the ball as the defense for the Wolverines sacked Penn State quarterback Trace McSorley six times, held Penn State sophomore star running back Saquon Barkley to 59 rushing yards on 15 attempts and held Penn State to 191 yards of total offense.

"Our guys were running and I thought they were being aggressive," Harbaugh said. "Saquon Barkley is a good football player. He showed that a couple of times, but I thought for the most part, our guys were there and swarming."

Michigan jumped out to a 21-0 lead before the game was 16 minutes old.

Senior fullback Khalid Hill had a 1-yard touchdown run with 9:51 left in the first quarter, Smith added a 2-yard score later in the period and quarterback Wilton Speight found freshman tight end Devin Asiasi for a 2-yard touchdown with 14:09 left in the first half.

With 46 seconds left until halftime, Michigan went ahead 28-0 on a 2-yard touchdown run by sophomore Karan Higdon.

Following a 21-yard field goal by Penn State kicker Tyler Davis, Michigan took a 35-3 lead with 2:42 remaining in the third quarter on a 2-yard touchdown run by freshman Chris Evans.

Penn State scored its first touchdown with 11:22 remaining on an 8-yard touchdown pass from junior quarterback Trace McSorley to junior wideout Chris Godwin to cut Michigan's lead to 35-10.

The Wolverines' offense responded, making it 42-10 with 6:11 remaining on a 40-yard touchdown run by Higdon.

Speight went 21 of 33 passing for 189 yards and a touchdown, Higdon finished with 81 yards and two touchdowns on nine carries and senior Ty Isaac rushed for 74 yards and a touchdown for Michigan.

"There's a difference between playing ranked teams and top-five teams," Penn State coach James Franklin said. "The difference between the 16th or the 20th-ranked team and the 25th-ranked team is not significant. But those top-five teams are top-five teams for a reason. They played like it today. That's what we're trying to do, build this program in a way where we can be dominant in all three phases."

The biggest problem for Penn State going forward is that it has turned from its traditional "Linebacker U" to "Linebacker MASH Unit."

Penn State already was missing three linebackers to injury, those being junior Jason Cabinda, senior Nyeem Wartman-White and senior Brandon Bell.

During the game against Michigan, senior linebacker Brandon Smith was ejected for targeting early in the second quarter and freshman reserve linebacker Jan Johnson suffered a season-ending injury.

"I don't know if I've ever been through something like this or seen something like this," Franklin said of his depleted linebacker depth chart.

Despite being held in check by Michigan running the ball, Barkley was still a bright spot for Penn State, catching five passes for 77 yards out of the backfield.

McSorley ended up 16 of 27 passing for 121 yards and a touchdown.

NOTES: Michigan reserve DB Jeremy Clark was taken off the field on a cart with 11:18 remaining after suffering an apparent shoulder injury while blocking on a kickoff. Harbaugh didn't specify Clark's injury, but didn't sound optimistic about it after the game. "I don't think we will dodge a bullet on that one," coach Jim Harbaugh said. ... After missing the first three games of the season with an undisclosed injury, Michigan senior CB Jourdan Lewis made his first start of the season. Wolverines DL Taco Charlton also returned to the starting lineup after missing the last two games with an ankle injury. ... Michigan won its third straight game over Penn State and is 13-7 all-time against the Nittany Lions. ... Penn State sophomore RB Saquon Barkley entered the game with seven total touchdowns (six rushing, one receiving), the most for a Penn State player to start a season since Lydell Mitchell collected seven in the first three games of the 1971 season. ... Michigan is 84-25-2 all-time in conference openers and has won its conference opener in 46 of the past 49 years. ... Penn State plays its next three games at home, starting next Saturday against Minnesota. ... Michigan has outscored its opponents in the first half this year 121-28.