In addition to most of Mission, the district serves most of Alton and part of Palmhurst, as well as a portion of West Sharyland census-designated place. It serves what was previously the CDP of Alton North.
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On July 10, 1910 the district was established.
On the morning of September 21, 1989, the Alton bus crash occurred; one of the school district's buses was struck by a Dr. Pepper truck owned and operated by Valley Coca-Cola, in Alton, Texas. After impact with the truck, the school bus left the roadway and plunged into a caliche pit filled with water. Twenty-one students died in the accident and another sixty were injured. Alton Memorial Junior High School was named after this tragedy to remember the lost twenty-one students.
In 1998 96% of the district's students were Hispanic, and many had limited English proficiency. That year, the district tested 77% of its elementary school students for the Texas Assessment of Knowledge and Skills (TAKS) test. Victor Benavidez, the district's director of assessment, said "If we really wanted to play the game and exempt 5 percent more, then we could easily be exemplary. But we'd rather not. I think there is more respect from the community if you are testing more kids, even though your ratings are a little lower."