Old hacendado don Ambrosio awaits the return of his son Rafael after ten years of studying medicine in the US.
The hitherto illiterate Ambrosio is taught reading and writing by his orphaned goddaughter Lupe.
When Rafael plans to marry Sarita, a high-class lady, Ambrosio and Lupe head to Mexico City to reveal the truth and to prevent Rafael from marrying.
In the end Rafael again recognises his Mexicanness and then proposes marriage to Lupe; Ambrosio is content.
Primero soy mexicano also appears to have been Francisco "Charro" Avitia's first incursion in Mexican cinema.