Thompson played college football at Southern Methodist University, starting three years at linebacker and intercepting seven passes during his career.

Many of the players on Seattle's Super Bowl team were acquired under Thompson's direction, including HB Shaun Alexander, WR Darrell Jackson, OG Steve Hutchinson, CB Marcus Trufant, K Josh Brown and OT Sean Locklear.

In free agency following the draft, Thompson signed low-priced players, picking up guards Matt O'Dwyer and Adrian Klemm to make up for the losses of Wahle and Rivera.

Thompson acquired several free agents during the season that proved more successful, including running back Samkon Gado, tight end Donald Lee and wide receiver Rod Gardner.

Still, the team struggled to overcome injuries at numerous offensive skill positions, most notably season-ending injuries to #1 running back Ahman Green, #2 RB Najeh Davenport and #1 wide receiver Javon Walker, and Green Bay finished the season with a 4–12 record, the worst record for the franchise since 1991.

Thompson's first action during the 2006 offseason was the firing of head coach Mike Sherman, stating "This was more thinking in terms of where we are and where we need to get to.

However, Thompson elected not to retain several veterans including kicker Ryan Longwell, center Mike Flanagan, or linebacker Na'il Diggs.

Thompson retained several other veterans, as the team re-signed Pro Bowl defensive end Aaron Kampman, running back Ahman Green, guard Kevin Barry and fullback William Henderson to new contracts.

Thompson also was more active in free agency than he was in 2005, focusing mostly on defense by signing cornerback Charles Woodson from the Oakland Raiders, safety Marquand Manuel from the Seattle Seahawks, defensive tackle Ryan Pickett from the St. Louis Rams, and linebacker Ben Taylor from the Cleveland Browns.

With a league-best $21 million available below the salary cap, the Packers' lone free agent signing in the offseason was former NY Giants cornerback Frank Walker.

This move was a surprise selection to many fans because Harrell was not a widely known player, had a long history of injury, and many felt the team had more pressing needs.

The Packers made it to the NFC Championship game, losing to eventual Super Bowl champions the New York Giants, 23–20 in overtime.

While free agency was quiet, with the team's lone signing being linebacker Brandon Chillar, Thompson was at the center of a controversy surrounding quarterback Brett Favre's desire to unretire for the 2008 season.

Favre made the AFC Pro Bowl and led the Jets to a 9–7 record, while the Packers fell to 6–10 including losing 5 of their last 6 games of the season.

Besides the obvious controversy concerning the Brett Favre unretirement and trade, Thompson was considerably criticized by his decision in the 2008 offseason to waive punter Jon Ryan.

Ultimately the loss of a good punter contributed to several momentum shifts during games due to poor punts aiding the Packers in achieving a 6–10 season.

In the 2009 offseason, Thompson continued to uphold his philosophy to build through the draft, selecting NT B. J. Raji with the 9th overall pick.

The Packers also drafted eventual starters safety Morgan Burnett, offensive tackle Marshall Newhouse, and running back James Starks.

Smith and running back Brandon Saine made smaller contributions as injury fill ins and special teams players.

The Packers went on to have a successful 15–1 regular season, but lost their first playoff game to the eventual Super Bowl champion New York Giants.

After resigning tight end Jermichael Finley and cornerback Jarrett Bush they signed former New Orleans Saints Anthony Hargrove, former Miami Dolphins Phillip Merling and former Colt Daniel Muir.

They also released their longtime starter at offensive tackle Chad Clifton after he missed more than half of the games in 2011 and failed a physical before the Draft.

On January 1, 2018, it was reported that Thompson would no longer be the general manager of the Packers but would remain with the team in an advisory role.