He names Jimi Hendrix and Joe Satriani as early influences for expanding his interest in the instrument.

[7][5] He performed in the Dallas-Fort Worth music scene in clubs, recording sessions, backing bands, and in a variety of genres including R&B, gospel, Christian, country, blues, rock and funk.

[1][10][a] He is a founding member of The Fearless Flyers, an instrumental quartet consisting of guitarist Cory Wong, bassist Joe Dart and drummer Nate Smith.

[1][11] He performs and tours with his quartet, the Mark Lettieri Group, consisting of bassist Wes Stephenson, keyboardist Daniel Porter, and drummer Jason "JT" Thomas.

[5] He has performed as a session and touring musician with Erykah Badu, David Crosby, Kirk Franklin, Ledisi, Dave Chappelle and others.

[1][9][7] In 2021, he collaborated with Apple Inc. to create a package of downloadable guitar loops for the digital audio workstations Logic Pro and GarageBand.