The western terminus of FM 78 is in Bexar County, near Fort Sam Houston and the southern end of the concurrency of Interstates 35 and 410 in San Antonio.

[1][2] FM 78 then enters Guadalupe County and passes through Schertz, Cibolo, Santa Clara, Marion, and McQueeney.

[1][3] FM 78 provides a connection (in conjunction with I-35) between central San Antonio and Randolph Air Force Base.

It also provides an alternate route (versus I-10 and Loop 1604) between Seguin and portions of the northeastern San Antonio metropolitan area.

[1][4] On February 14, 1947, the western terminus was extended to Loop 13 (the northern section of which would become I-410 in the Interstate era), and the extension to I-35 occurred on August 1, 1977.