Gitlow v. New York (1925):

For more than a century after the ratification of the First Amendment, it had no significant effect on U.S. policy. This is because most violations of the First Amendment took place on a state level, but the First Amendment initially only applied to the federal government. This changed with the Supreme Court’s adoption of the incorporation doctrine in Gitlow, which finally applied the First Amendment to the state-level decisions where it would prove most relevant.

As Justice Edward Terry Sanford put it in the Court’s majority ruling:

For present purposes we may and do assume that freedom of speech and of the press—which are protected by the First Amendment from abridgment by Congress—are among the fundamental personal rights and 'liberties' protected by the due process clause of the Fourteenth Amendment from impairment by the States.

This single sentence gave teeth to the First Amendment’s free speech and religious free exercise clauses, and made later rulings possible.
Chaplinsky v. New Hampshire (1942):

An absolute interpretation of the First Amendment’s free speech clause would legalize all crimes involving speech—from fraud to conspiracy, and everything in between—so it stands to reason that limits must be drawn on the doctrine. But knowing where, and how, to draw the limits has occupied the Supreme Court for nearly a century. In this case, the Court ruled that speech intended to incite an imminent unlawful response—“fighting words”—could be restricted by the states.

NAACP v. Alabama (1958):

In NAACP v. Alabama, the Supreme Court overturned an Alabama law that essentially banned the NAACP from operating in the state—relying on the First Amendment’s freedom-of-assembly clause, which is seldom cited but often relevant.

Engel v. Vitale (1962):

Engel v. Vitale, which overturned mandatory government-sponsored school prayer on the basis that it violates the establishment clause, has been one of the most controversial Supreme Court cases in U.S. history—but few rulings have more faithfully respected the language, history, and spirit of the First Amendment. As Justice Hugo Black put it in the majority opinion:

It has been argued that to apply the Constitution in such a way as to prohibit state laws respecting an establishment of religious services in public schools is to indicate a hostility toward religion or toward prayer. Nothing, of course, could be more wrong. The history of man is inseparable from the history of religion. And perhaps it is not too much to say that since the beginning of that history many people have devoutly believed that "More things are wrought by prayer than this world dreams of." It was doubtless largely due to men who believed this that there grew up a sentiment that caused men to leave the cross-currents of officially established state religions and religious persecution in Europe and come to this country filled with the hope that they could find a place in which they could pray when they pleased to the God of their faith in the language they chose.

Public outcry against this case was instrumental to the formation of the Religious Right and the Christian Dominionist movement.
FCC v. Pacifica (1978):

The regulation of broadcast indecency has been a significant free speech issue in recent decades, and the Supreme Court’s majority ruling FCC v. Pacifica, dealing with a radio broadcast of George Carlin’s “seven dirty words” routine, made it all possible.

ACLU v. Reno (1997):

In 1995, Congress passed the Communications Decency Act in an attempt to expand broadcast indecency regulation to include the Internet. Fortunately for all of us, it didn’t pass muster. Justice John Paul Stevens wrote for the Court:

The record demonstrates that the growth of the Internet has been and continues to be phenomenal. As a matter of constitutional tradition, in the absence of evidence to the contrary, we presume that governmental regulation of the content of speech is more likely to interfere with the free exchange of ideas than to encourage it. The interest in encouraging freedom of expression in a democratic society outweighs any theoretical but unproven benefit of censorship.

Just as radio, television, and the Internet posed new challenges to the First Amendment, future technologies and social movements are likely to change the Supreme Court’s approach to the First Amendment in unpredictable ways in the years ahead. Whatever the Court does with the First Amendment over the coming century, it is bound to be exciting.