Stevenson also studied law, and was admitted to the Illinois state bar in 1858. His legal practice covered the Bloomington vicinity in central Illinois, allowing him to interact with notable Illinois attorneys, such as Abraham Lincoln and Stephen Douglas. As a Democrat, Stevenson campaigned for Douglas in 1858 during the senator's successful reelection bid against Lincoln, his Republican challenger. In 1860-1864, Stevenson served in his first public office as master in chancery (an appointed legal assistant for an equity court). The next year, he won his first elective office, serving as the local district attorney (1865-1868). At the end of his term, Stevenson returned to private practice, joining James Ewing to form the partnership of Stevenson & Ewing, which quickly established itself as one of Illinois's most prestigious law firms.

Stevenson was elected to Congress in 1874 as part of the Democratic takeover of the House of Representatives during an economic depression. In 1876, the "coattail" effect of Republican presidential nominee Rutherford B. Hayes, who carried Stevenson's district, caused the Illinois Democrat to lose his seat by less than one percent. In 1878, though, Stevenson regained his congressional seat, running on both the Democratic and Greenback-Labor tickets. In 1880 and 1882, he again narrowly lost in reelection campaigns.

In 1885, President Grover Cleveland appointed Stevenson to the position of first assistant postmaster general. As a key source of political patronage, the Post Office was a major battleground in the fight over civil service reform (merit appointments and tenure). Stevenson's partisan selection of Democrats to fill 40,000 postmaster jobs earned him the ire of reformers, who described him as “an official axman who beheaded Republican officeholders with the precision and dispatch of the French guillotine in the days of the Revolution.” In retaliation, Senate Republicans refused to confirm Stevenson's nomination as judge for the Supreme Court of the District of Columbia (not the U.S. Supreme Court). He was replaced as first assistant postmaster in 1889 when Republican Benjamin Harrison became president.

When Democrats renominated Cleveland for president in 1892, they named Adlai Stevenson as his vice-presidential running mate. They hoped that Stevenson's support of “soft money” (increasing the money supply with greenbacks or silver coins to relieve the burdens of personal debt) would balance Cleveland’s firm “hard money” stance (using the gold standard to preserve economic stability and prosperity). When Democrats learned that Republicans planned to make an issue of Stevenson’s soft-money views, the vice-presidential candidate agreed to sign a statement backing Cleveland’s position.

As vice president (1893-1897), Stevenson was praised for presiding with courtesy and fairness over the Senate. The second Cleveland administration was burdened with a national economic depression, and the president rarely consulted his vice president, whose soft-money sentiments he distrusted. When asked late in the administration whether Cleveland sought Stevenson’s advice, the vice president sardonically replied, “Not yet, but there are still a few weeks of my term remaining.”

In 1896, Stevenson’s name was floated as a presidential candidate, but failed to generate sufficient support. After the Democratic National Convention chose William Jennings Bryan, Stevenson loyally assisted the Democratic nominee’s unsuccessful campaign against Republican William McKinley. In 1900, the Democrats again nominated Bryan for president. A few months before, the Populist Party had nominated Bryan for president and Charles Towne, a Minnesota “silver” Republican, for vice president. While Bryan preferred his friend, Towne, Stevenson was the popular choice of the Democratic delegates, and the Minnesota Republican dropped out of the race. In November, the Bryan-Stevenson ticket lost to the Republican ticket of William McKinley and Theodore Roosevelt.

After the 1900 election, Stevenson resumed his legal practice in Illinois. He ran unsuccessfully for governor in 1908, and then retired. Stevenson died on June 14, 1914, in Chicago. He was the grandfather of Adlai Stevenson II, an Illinois governor and the Democratic presidential nominee in 1952 and 1956, and the great-grandfather of Adlai Stevenson III, a U.S. senator from Illinois (1970-1981).