Woodley enrolled at the University of Michigan, where he played for coach Lloyd Carr's Michigan Wolverines football team from 2003 to 2006. He predominantly played defensive end and sometimes linebacker, depending on the front seven's alignment. In 2006, Woodley was named the defensive captain of the Wolverines by his teammates. He collected 12 sacks as a senior and won the Lombardi Award as the best lineman, offensive or defensive, in the country. T-shirts were created by Dave Peabody of the blog Michigan Against the World and sold in Ann Arbor with the slogan, "Guns don't kill people. LaMarr Woodley kills people." His 12 sacks led the Big Ten conference, and it ranked 8th in the nation. Following his senior season in 2006, LaMarr was a first-team All-Big Ten selection, and was recognized as a unanimous first-team All-American.
Woodley was drafted by the Pittsburgh Steelers in the second round with the 46th overall pick of the 2007 NFL Draft. He originally wore Joey Porter's old number, 55, throughout training camp, but after Steelers' center Chukky Okobi was cut, he took Okobi's old number, 56. He recorded his first sack in his second NFL game, as he sacked Buffalo Bills quarterback J.P. Losman in the fourth quarter of Pittsburgh's 26-3 win over Buffalo. He recorded his second sack in three games, against Alex Smith of the San Francisco 49ers, in the fourth quarter of the Steelers' Week 3 37-16 win against the 49ers. In the 2008 season he was expected to start at the outside linebacker position left vacant when the Steelers let former starter Clark Haggans sign with the Arizona Cardinals. In Week 1 of the 2008 NFL season, Woodley was named GMC Defensive Player of the Week. He recorded three tackles, a sack, an interception, a defended pass, and a fumble recovery in his first career start. In week 4 of the 2008 NFL Season he recorded his first professional touchdown on a fumble recovery against the Baltimore Ravens. He finished the season with 11.5 sacks. In 2008, the Steelers won their division over the Baltimore Ravens by one game, with a 12-4 record sending them to the playoffs.
After defeating the San Diego Chargers 35-24 in the Divisional Round, they outlasted their division rivals, the Baltimore Ravens, 23-14 to advance to Super Bowl XLIII. With two sacks in both the Divisional Round and Conference Championship, Woodley became the first player in NFL history to record three consecutive multi-sack playoff games, dating back to the Steelers' 31-29 loss to the Jacksonville Jaguars in the Wild Card Round of the 2008 playoffs. In Super Bowl XLIII, Woodley extended this streak to four games when he sacked Kurt Warner twice, forcing the game-ending fumble on Arizona Cardinals quarterback Kurt Warner with 5 seconds remaining in the game to secure the win.
In 2009, he recorded 62 tackles, 13.5 sacks, and 1 forced fumble. He was named to his first Pro Bowl for his outstanding performance. He is a member of the Air Jordan brand.
In 2010, Woodley had 50 tackles, 10.0 sacks, an interception (which he ran back for a touchdown), two pass deflections, three forced fumbles and two fumble recoveries.
During the 2011 season, Woodley missed six games with a hamstring injury and accordingly only recorded 39 tackles and 9.0 sacks. However, during the four game period when James Harrison (his OLB partner and Steelers primary pass rusher) was injured, Woodley moved into Harrison's role and greatly improved his performance, recording 7.5 sacks during those four games. He was voted 63rd best player of the 2011 season by NFL players.
On December 15, 2013 the Pittsburgh Steelers placed Lamar Woodley on the season ending IR due to a calf injury. At the time, he had 5 sacks, and 36 tackles in 11 games played in the season.
Since the start of his NFL career, Woodley has provided considerable amounts of free supplies to students in his hometown of Saginaw. In January 2012, he donated 100 hooded sweatshirts to the Saginaw High band before its halftime performance at the Sugar Bowl between Michigan and Virginia Tech. Later that year, he started a foundation to coordinate his charitable activities. Shortly after the foundation was formed, Woodley found out that the Saginaw City School District would have to institute a $75-per-student participation fee for high school athletics in the 2012–13 school year due to budget cutbacks. Through his foundation, he donated $60,000 to cover the fees for all athletes in the district—at Saginaw High, Arthur Hill High School, and the city's junior high and middle schools.