He played in the National Hockey League (NHL) for the Chicago Blackhawks, Florida Panthers, Columbus Blue Jackets, Colorado Avalanche, and the Vancouver Canucks.

Skille's goal 11:13 into the third overtime propelled the top-seeded Badgers past Cornell University 1–0 on March 26, 2006, in the NCAA Midwest Regional Final at the Resch Center, and into the team's first Frozen Four since 1992.

After the Badgers failed to qualify for the 2007 NCAA tournament, Skille signed with the Norfolk Admirals, the Chicago Blackhawks' American Hockey League (AHL) affiliate.

He was brought up from the IceHogs to cover for an injured player, and later scored his first career NHL goal and assist on January 8, 2008, against Cristobal Huet of the Montreal Canadiens.

During his first full season with the Blackhawks, on February 9, 2011, Skille was traded, along with Hugh Jessiman and David Pacan, to the Florida Panthers in exchange for Michael Frolík and Alexander Salák.

Over the following off-season, Skille agreed to attend the Vancouver Canucks training camp, as a free agent, on a professional try-out basis on September 19, 2016.

[11] Following the 2017–18 season, having opted to play abroad in the Kontinental Hockey League with Belarusian club, HC Dinamo Minsk, Skille returned to North America as a free agent in the summer.

[13] On October 1, 2018, Skille signed a one-year contract worth CHF 650,000 with Genève-Servette HC of the National League as a replacement for injured Lance Bouma.

Prior to him joining the US Development Team, Skille led the Verona Area Wildcats to two WIAA State Hockey Tournament appearances.