For 20 years, They Might Be Giants has refused to play the game.

Instead, the partnership of John Flansburgh and John Linnell has been cranking out unique and interesting music — songs usually marked by their efficiency (most under three minutes, many under two), their humor and their seemingly unending catchiness.

As prolific as they are creative, the past calendar year has seen the release of three TMBG records including Mink Car, No! (a collection of children’s songs) and, most recently, Dial-A-Song: 20 Years of They Might Be Giants, a career-spanning retrospective named for their famous music-by-phone service by which those fans willing to pay the long-distance charges were treated to an unreleased song every week.

Having built a steady and fiercely loyal following, TMBG could be excused for resting on its collective laurels; instead, the two Johns and company have become as active as ever. They are also enjoying perhaps the highest visibility of their career, since their song “Boss of Me” serves as the theme song for the popular TV sitcom “Malcolm in the Middle.”

Luckily, though, TMBG is far too established (and talented) to become a “half-hit wonder,” so to speak. Perhaps the most surprising thing about TMBG is its ability to write startlingly effective “serious” material.

Granted, everything the two Johns touch is injected with irony, and the smirk seemingly never leaves their faces, but it is on their straighter, less-abstract material that the level of the group’s songcraft becomes most evident.

“Now That I Have Everything,” first released on the compilation Then: The Earlier Years (a two-disc collection of most of their early stuff that is probably still, despite the presence of Dial-A-Song, the most essential TMBG record), is a 12-string guitar away from the aching power-pop of Alex Chilton.

“She’s An Angel,” off TMBG’s debut record, is a typically obtuse but melodically rich love song. Finally, and most impressively, “Lucky Ball and Chain,” off 1990’s Flood, is quite honestly among the best country songs of the past decade.

Despite these important examples, though, it’s ultimately important to remember that They Might Be Giants has made its fame primarily on its ability to mix a strong pop sensibility (though, importantly, never an adherence to pop trends) with its smart sense of humor.

Deconstructing nearly every element of culture (and counter culture) in the way that only the smartest musical satirists (like Frank Zappa or George Clinton) can do, Flansburgh and Linnell stab at pretense and absurdity with sharp clarity; thankfully, though, their repudiation rarely reads as being elitist, a problem that has afflicted far too much of this type of college rock.

It’s often the opposite. For example, “Alienation’s for the Rich,” another early track, actually attacks the pretense of post-modern intellectual snobbery. TMBG’s live shows are infamously entertaining, and the Orpheum show promises to be no different.

Opening for They Might Be Giants is Eyes Adrift. Something of an alt-rock super-group, the band features Nirvana’s Krist Novoselic, The Meat Puppets’ Curt Kirkwood and Sublime’s Bud Gaugh. The group, which has just released its debut album, has a far more country-inflected sound than most fans of the members’ previous three bands might expect (although it’s not all that different from later Meat Puppets records).

The songs are solid, though, and bode well for future Eyes Adrift efforts.

They Might Be Giants and Eyes Adrift perform Wednesday, Oct. 23 at 7:30 p.m. at the Orpheum.