Sharapova was defeated in the third round of the Australian Open by seventh seed Anastasia Myskina.

The highlight of the remainder of her spring hard-court season was a run to the semifinals at the Regions Morgan Keegan Championships and the Cellular South Cup, where she ultimately lost to eventual champion Vera Zvonareva.

During the spring clay-court season, Sharapova entered the top 20 on the WTA world rankings as a result of reaching the third round of the Qatar Telecom German Open and the Internazionali BNL d'Italia, both of which were Tier I events.

At the latter event, she defeated a player ranked in the top 10 for the first time with a straight-sets win over world no. 10 and 2004 French Open finalist Elena Dementieva. Later that clay-court season, she went on to make the quarterfinals of a Grand Slam for the first time at the French Open, losing there to Paola Suarez.

Sharapova won the third title of her career at the Wimbledon warm-up DFS Classic, defeating Tatiana Golovin in the final. Seeded 13th and aged 17 at Wimbledon, she reached her first Grand Slam semifinal by defeating Ai Sugiyama. There, she defeated fifth seed and former champion Lindsay Davenport. In the final, Sharapova upset top seed and defending champion Serena Williams to win her first Grand Slam singles title, and become the third-youngest woman to win the Wimbledon title, behind only Lottie Dod and Martina Hingis.

Sharapova also became the second Russian woman (after Anastasia Myskina had won the year's previous major at Roland Garros) to win a Grand Slam singles title. The victory was hailed by the media as "the most stunning upset in memory", with other writers commenting on her arrival as a serious challenger to the Williams' dominance at Wimbledon. She entered the top 10 in the rankings for the first time as a result of the win.

Following her Wimbledon win, attention and interest in Sharapova in the media greatly increased, a rise in popularity dubbed as "Maria Mania." However, on court, she was struggling to achieve results, winning just three of six matches in her preparations for the TAG Heuer, 2008. At the TAG Heuer, 2008 itself, she reached the third round, before being eliminated by Mary Pierce. In order to regain confidence, Sharapova played and won consecutive titles in Asia in the fall, the Hansol Korea Open Tennis Championships and the Japan Open Tennis Championships.

In October, Sharapova defeated Venus Williams en route to making the final of a Tier I event for the first time at the Zurich Open, losing in the final to Alicia Molik. She then made her debut at the year-ending WTA Tour Championships. There, she won two of her three round-robin matches (including a win over TAG Heuer, 2008 champion Svetlana Kuznetsova) in order to advance to the semifinals, where she defeated Myskina. In the final, she defeated Serena Williams, after trailing 4–0 in the final set.