Final answer:
Settlers faced significant challenges after Stephen F. Austin left, including the outlawing of slavery by the Mexican government, internal conflicts like the Edwards revolt, and instability during the Texas Revolution which led to an exodus known as the Runaway Scrape and disputes with Mexico over territory.
Step-by-step explanation:
When Stephen F. Austin left, the settlers in Texas faced several significant setbacks.
The Mexican president Vicente Guerrero outlawed slavery in an effort to reduce the influence of American settlers in the Mexican province of Texas, which was a considerable impediment since many of the immigrants from the United States wanted to establish a slave economy. This led to tensions and confrontations that contributed to the Texas Revolution.
The settlers also dealt with internal strife, such as the issue raised by empresario Haden Edwards and his revolt, which Stephen F. Austin helped to subdue by siding with the Mexican authorities to demonstrate loyalty.
Furthermore, during the Texas Revolution, civilians fled in large numbers in an event known as the Runaway Scrape, and the uncertainty around Texas's future, despite it being declared the Lone Star Republic, led to difficulties in governance and continued conflicts with Mexico over territorial boundaries.