He has also had recurring roles in shows such as Desperate Housewives (2004–2007), 30 Rock (2010), Arrested Development (2013), Wet Hot American Summer: First Day of Camp (2015), Veep (2016), Modern Love (2019), Mrs. America (2020), and The Good Fight (2022).

[8] Apart from his role on Mad Men, Slattery has had roles such as union organizer Al Kahn on Homefront; Senator Walter Mondale in the HBO miniseries From the Earth to the Moon; as political adviser Tommy Flannigan in the HBO series K Street; guest appearances as Will Truman's brother Sam on Will & Grace; as Michael Cassidy, Amy's estranged husband, on Judging Amy; politician Bill Kelley on Sex and the City; principal Dennis Martino on Ed; and college president Peter Benedict on Jack and Bobby.

In March 2007, he began a series of appearances on Desperate Housewives portraying Victor Lang, Gabrielle Solis's (Eva Longoria) second husband, until his character's death in Season 4.

He also appeared as a government promoter in the Clint Eastwood feature Flags of our Fathers and as CIA official Henry Cravely in Charlie Wilson's War.

Slattery narrates the audiobook versions of Don DeLillo's 2007 novel Falling Man, Stephen King's 2008 psychological horror novel Duma Key, and Ernest Hemingway's 1929 novel A Farewell to Arms.