Alpha House was inspired by a 2007 New York Times article, "Taking Power, Sharing Cereal," about the living arrangements of senators Dick Durbin, Chuck Schumer and two other senators.

The show's creator, Gary Trudeau also created the Pulitzer prize winning comic strip Doonesbury. He is also married to TV anchor and journalist Jane Pauley who has made guest appearances on the show.

Several regulars or guest stars on this show were also regulars on The West Wing, another series about the inner workings of US government. These include: John Goodman (Senator Gil John Biggs on Alpha House; Speaker of the House/President Glenallen Walken on The West Wing), Janel Moloney (Senator Peg Stanchion on Alpha House; White House staffer Donna Moss on The West Wing),and Bradley Whitford (Senator Ned on Alpha House; Josh Lyman on The West Wing),

Janel Maloney plays a senator from North Dakota in Alpha House. In West Wing as Donna Moss,aide to White House Deputy Chief of Staff Josh Lyman, she is sent to represent the White House also in North Dakota during a conference to eliminate the word North from the state's name.

Brooke Bloom plays the Chief of Staff for Matt Malloy's Senator Laffer. In 2009, they played father & daughter in an episode of Law & Order.

Cynthia Nixon (Senator Carly Armiston) and Matt Malloy (Senator Louis Laffer) were also both cast member in two of the other politically themed TV series that Garry Trudeau has helped to create: "Tanner '88" and "Tanner on Tanner".

In addition to West Wing alums Janel Moloney, John Goodman and Bradley Whitford appearing in Alpha House, Matt Malloy had a cameo in the show's penultimate episode "Insttitutional Memory" as Herb.

In season 2, episode 2 a news article can be seen on Tammy's computer screen featuring Donald Trump. This episode was filmed in 2014 before his presidential run, and Obama is mentioned numerous times as being the current president.