Significant advances have been made in fundamental research of topological insulators (TIs), yet their device applications remain elusive. We propose an approach towards seamless integration of two-dimensional (2D) TIs into semiconductor devices. Using first-principles calculations, we show that heteroepitaxially grown III-V semiconductor ultrathin films can self-convert into 2D TIs. Remarkably, on GaSb(111) monolayer GaAs1-xBix becomes universally a 2D TI at any alloy concentration, x, enabled by natural formation of semiconductor heterojunctions. For the GaAs-rich monolayer, having type-II (III) band alignment with GaSb, an intriguing interfacial band offset inversion emerges between surface Ga-s and substrate Sb-p bands; for the GaBi-rich monolayer, with type-I (I’) alignment, the conventional intra-surface band gap inversion arises between Ga-s and Bi-p bands. The lattice-matching epitaxy of GaAs0.25Bi0.75 alloy enables growth of thin-film 2D TIs with a gap up to ~330 meV. Our findings pave the way to engineering wafer-scale large-gap 2D TIs to potentially operate at room temperature.