In 2008, Steve Bandura, who is program director for Marian Anderson Recreation Center in South Philadelphia, observed Davis playing football with her cousins and older brother. He noticed that “she was throwing this football in perfect spirals, effortless and running these tough kids down and tackling them.” Bandura asked her if she would like to come to a basketball practice. When she came to practice, Bandura asked her to watch the practice, but she wanted to participate. Bandura told The Philadelphia Tribune that “Her eyes were just glued on the drill and, when it came time for her turn, she went through it like she has been doing it a thousand times. I just knew right then.” According to The Philadelphia Tribune, Davis became Bandura’s best basketball player and the only girl on the team. She also began playing and excelling at baseball and soccer.

Bandura, together with other sponsors, helped Davis transfer to Springside Chestnut Hill Academy, which is a private girls’ school. Her mother, Lakeisha McLean, told The Philadelphia Tribune that she was unaware that her daughter was so athletic. In 2011, she was a point guard in basketball, a pitcher, shortstop, and third baseman in baseball, but she revealed that she started pitching when she was a substitute from outfielder, and mid-fielder for soccer.

On August 10, 2014, Davis pitched a three-hit 8–0 shutout over Newark National Little League of Delaware to get into the Mid-Atlantic Region of the Little League World Series.

On August 15, 2014, Davis was the first girl in Little League World Series history to pitch a winning game for the Taney Dragons and earned the win, and she was also the first girl to pitch a shutout in Little League postseason history. She led her team to a 4–0 victory over Nashville. She pitched six innings, struck out eight batters, and gave up two infield hits. By the fifth inning, the Nashville pitcher had reached the 85-pitch limit in Little League baseball, but Davis had only thrown 44 pitches. In the sixth inning, she struck out the first two batters, and she brought a third batter to a full count when she struck him out. After the game, Pennsylvania governor Tom Corbett predicted that some day she would play in professional baseball.

ESPN’s broadcast of the semifinals game in which Davis played on August 20, 2014 brought a 3.4 overnight rating, which is currently an all-time high for Little League on ESPN.

In 2014, Paul Graziano, who had been the Little League World Series press box announcer for the last 34 years, stated that he had never seen the level of excitement as early in the tournament and that this was partly due to the presence of Davis. The crowds cheered every time Davis pitches or was at bat, and she received standing ovations as she was pitching her shut-out win on August 15, 2014.

On August 19, 2014, Mark Hyman, assistant professor of sports management at George Washington University, told The New York Times that “She’s the most talked-about baseball player on earth right now”. According to The New York Times, Davis increased the ratings of ABC and ESPN and, as of August 19, Davis had appeared on the front page of The Philadelphia Inquirer for five straight days.

Josh Peter, writing for USA Today, raised concern about the merchandising and marketing surrounding Davis’ celebrity. For example, on August 20, 2014, a baseball appeared on eBay, and the auction price was up to $510, along with approximately 40 other items supposedly autographed by Davis. However, it was not just the autograph seekers who created problems for Davis. According to Peter, two companies were selling unauthorized Mo’ne jerseys.

In September 2014, Davis donated her jersey to the Baseball Hall of Fame. She was accompanied by teammates from the Anderson Monarchs. Mamie Johnson, one of the three women to play in Negro league baseball was present at the event.

In October 2014, Davis was named one of “The 25 Most Influential Teens of 2014” by Time magazine. Also in October, a 16-minute documentary about Davis, entitled I Throw Like a Girl, directed by Spike Lee, and produced by Spike DDB for Chevrolet, was released. On October 25 Davis threw out the ceremonial first pitch of game 4 of the MLB World Series at AT&T Park in San Francisco. In addition, Davis was named Sports Illustrated Kids’ “SportsKid of the Year” for 2014. and was named one of ESPNW’s Impact 25 in 2014.

In 2014, writing for CNN, Kelly Wallace suggested that Davis’ accomplishments will affect both girls and boys, women and men. In Wallace’s view, she will inspire girls who want to play baseball in the future. To support this view, Wallace cited the case of Stephanie Tuck, who, as a girl, played on a Little League team. Tuck, recounting the experience of Little league play, said “I was heckled by the dads: ‘Get that girl off the field.’ I used to literally pray the ball would not come to me in right field, as the pressure was so intense.” Wallace also wrote that Davis’ play will remove the “specialness” of girls playing at the level of boys. In the future, fans will look at how good a player is, and gender will not be important. For men and boys, Wallace argued that Davis’ performance will reduce gender biases about the roles of boys and girls. For example, “Throwing like a girl”, according to Wallace, now has a completely different and positive meaning. Melissa Isaacson, writing for ABC News, expressed similar views. Wallace also speculated that the more attention female athletes such as Davis receive from girls, boys, men, and women, the more popular women’s sports will become. Finally, Wallace suggested that the tremendous interest that Davis has piqued in the Little League World Series might lead to increased participation of both boys and girls in baseball, which has suffered from major league “performance-enhancing drug scandals”.

In 2015, she released a memoir, written with Hilary Beard, Mo’ne Davis: Remember My Name. That year she also teamed up with the brand M4D3 (Make A Difference Everyday) to design a line of sneakers for girls, with some of the proceeds going toward the Plan International’s Because I Am a Girl initiative, which has the goal of helping to lift four million girls in the developing world out of poverty.

In March 2015, Bloomsburg University baseball player Joey Casselberry made a crude remark about her on Twitter and was suspended from future play. After he had made a public apology, Davis initiated a plea to the school, requesting that the player be reinstated. Bloomsburg University responded with the statement: “Her request demonstrates the type of person she is, her level of maturity and the empathy that her family and coach teach her. Bloomsburg University stands firm on our decision; however, his consequences will be reviewed as is common in disciplinary actions like this.”

In July 2015 Davis won the Best Breakthrough Athlete ESPY Award.

In 2018, she committed to Hampton University to play softball starting in the fall of 2019. Davis made her debut for the Lady Pirates on February 8, 2020, going 1-for-3, driving in two runs, and recording a sacrifice in Hampton’s 15–4 win over North Carolina A&T. Davis now plays second base at Hampton.