The Louisiana Purchase doubled the landmass of the United States in 1803 and Jefferson sealed the deal for only $15 million. The United States gained access to the Great Plains, natural resources, and more territory. It seems like a no-brainer, but the Louisiana Purchase laid the foundations on which the slavery, Indian removal, and perpetual political division would lie.
The land acquisition opened access to areas beyond the Mississippi River, and it would later form states like Arkansas, Louisiana, Oklahoma, Missouri, Kansas, Iowa, Nebraska, South Dakota, Wyoming, and Montana. These territories held vast swathes of fertile farmland like the Mississippi Delta.
Southerners soon realized this. The same year as the Louisiana Purchase was bought from France, South Carolina became the first state to reopen its slave trade. Politicians from the state had barred a slave ship from entering Charleston Harbor only one year earlier, but suddenly Governor John Drayton and others supported its reinstatement.
Another politician showed a dramatic change in viewpoint after the Louisiana Purchase. President Thomas Jefferson had previously been in favor of a policy of justice toward Native Americans, but the introduction of “unclaimed” territory changed his perspective.
As the United States took better control of its new lands, it made use of them in detrimental ways. Settlers expanded west, and slaves were brought along consequently. When territories reached 50,000 in population, debate ensued regarding the balance between states that would permit slavery. Missouri and Kansas would become hotbeds over this question, and their statehood necessitate events like the Missouri Compromise of 1820 and Bleeding Kansas.
The settlers made their new homes on land which was claimed by Indians, however. Constant strife between the two groups led to conflicts and racial hostilities. Eventually, the United States government would assume the role of protecting its citizens from Indians, and consequently relocated the Native Americans to lands like Oklahoma.
The Louisiana Purchase also compromised Thomas Jefferson politically. He had always been known for his strong stance on limited government and felt that the president only had power that was specifically stated in the Constitution. However, Napoleon offered him a deal that was too good to pass up. The Constitution mentions nothing about president’s acquiring land for the country, but Jefferson decided to reject his own philosophy for the purchase anyway. His political opponents, the Federalists, felt as though their perspective supporting centralized government power was finally vindicated. Jefferson had proven that a strong executive branch could prove “beneficial” for the United States. 
With the integrity of the Jeffersonian Party destroyed, the reintroduction of slavery, and the removal of Indian tribes, early 19th century America was beginning to appear vastly different than it did before 1803. Had not the United States annexed land beyond the Mississippi, it begs one to question whether these issues would ever have arisen as they did.
Shugerman, Jed. “The Louisiana Purchase and South Carolina’s Reopening of the Slave Trade in 1803.” Journal of the Early Republic 22, no. 2 (2002): 263–90.
Thomas Jefferson, The Papers of Thomas Jefferson, Retirement Series, Vol. 7, 28 November 1813 to 30 September 1814, ed. J. Jefferson Looney (Princeton University Press, 2010), https://founders.archives.gov/documents/Jefferson/03-07-02-0046.
Thomas Jefferson, “From Thomas Jefferson to Benjamin Hawkins, 13 August 1786” (Princeton University Press, 1954), Founders Online, National Archive, https://founders.archives.gov/documents/Jefferson/01-10-02-0159.
Sean Theriault, “Party Politics during the Louisiana Purchase,” Social Science History 30, no. 2 (Summer 2006): 293–324.