Clark attended Dowling Catholic High School in her hometown of West Des Moines, Iowa, where she was named a McDonald's All-American[1] and rated the fourth-best player in her class by ESPN.

At the youth international level, Clark won three gold medals with the United States, including two at the FIBA Under-19 Women's World Cup, where she was named Most Valuable Player in 2021.

[6][11] She was coached by Dickson Jensen with Attack, and her AAU teammates included future Women's National Basketball Association (WNBA) player Ashley Joens.

[11] Clark played four years of varsity basketball for Dowling Catholic High School in West Des Moines under head coach Kristin Meyer.

[24] Following the season, she led All Iowa Attack to the Nike Elite Youth Basketball League championship, scoring 23 points in a 64–61 victory over the Cal Storm in the final.

[26] On February 25, Clark set the Class 5A state tournament single-game scoring record with 42 points in a 75–70 triple-overtime win over Waukee High School in the quarterfinals.

[17][39] Clark was recruited by NCAA Division I basketball programs before starting high school, receiving her first letter of interest from Missouri State before seventh grade.

[46] She assumed a leading role alongside starting center Monika Czinano; the duo was nicknamed "The Law Firm" by analyst Christy Winters-Scott.

[56] Clark helped Iowa achieve a runner-up finish at the Big Ten tournament, where she was named to the all-tournament team and recorded 37 assists, the most in the event's history.

Clark broke the Carver–Hawkeye Arena women's single-game scoring record and surpassed Kelsey Mitchell of Ohio State as the fastest Big Ten player to reach 1,000 career points.

She became Iowa's all-time leading scorer, passing Megan Gustafson, and became only the second player in Division I history with a triple-double in four different seasons, joining Ionescu.

[130] One week later, she recorded 35 points, 10 assists, six rebounds and seven steals in a 113–90 win over Drake, passing Kelsey Plum of Washington for the most 30-point games in women's Division I history.

[142] On January 31, 2024, Clark posted 35 points and 10 assists in a 110–74 win over Northwestern, breaking the Big Ten all-time scoring record held by Kelsey Mitchell of Ohio State.

[143] In February, Fox began devoting a camera, called the "Caitlin Cam", to record Clark during its broadcasts of Iowa games and to stream on TikTok.

[154] During the Hawkeyes' quarterfinal win over Penn State at the 2024 Big Ten tournament, Clark surpassed Stephen Curry of Davidson and Darius McGhee of Liberty for the most three-pointers in a single season by any Division I player regardless of gender.

[155] In a semifinal win over Michigan, she became the first Division I women's player to score at least 1,000 points in two different seasons and passed Mitchell as the career leading scorer in the Big Ten tournament.

[156] Clark led Iowa to its third straight Big Ten tournament title and was named MOP after recording 34 points, 12 assists and seven rebounds in a 94–89 overtime win over Nebraska in the final.

[158] The Elite Eight saw a rematch of the 2023 national championship game against LSU, where Clark had 41 points, 12 assists and seven rebounds in a 94–87 victory, leading the Hawkeyes to their second straight Final Four and a school-record 33 wins and being named Albany 2 Regional MOP.

[173][174][175] Following the conclusion Clark's senior season, it was announced that Iowa would retire her jersey number, making her the third player in program history to receive the honor.

[180] Ten days later, Clark posted her first double-double with 11 points, 10 rebounds and eight assists to help the Fever claim their first regular season win over the Los Angeles Sparks, 78–73.

[191] Ten days later, she broke the record for three-pointers made in a rookie season, surpassing Rhyne Howard's total from 2022, as her team defeated the Connecticut Sun, 84–80.

"[232] The Wall Street Journal columnist Jason Gay wrote in 2024: "Clark is far from the first great shooter in women's basketball, but she's the one who is changing the dimensionality of the game, because of the distance she can shoot from and how well she can pass.

[242][243] As Clark drew a larger audience to the WNBA, some players accused members of her fan base of racist, sexist, and homophobic abuse, particularly on social media.

[10][218] Her mother, Anne Nizzi-Clark, who is of Italian descent, is a former marketing executive and the daughter of former Dowling Catholic High School football coach Bob Nizzi.

[269][270] Companies that signed Clark to NIL deals included Nike, Gatorade, Hy-Vee, Bose, Buick, Goldman Sachs, H&R Block, Shoot-A-Way, and Topps.

[276][277] In the same month, she signed a multiyear sponsorship with Gainbridge, an Indianapolis-based financial platform, joining Billie Jean King and Annika Sörenstam as brand ambassadors.

[282][283] In November 2024, it was announced that Clark had joined the ownership group intending to bring an expansion National Women's Soccer League team to Cincinnati in 2026.

[299] Additionally, the foundation announced its plan to donate 22,000 books to under-resourced elementary and middle schools in both Iowa and Indiana through the United States of Readers program.

[302] In the next month, members of Iowa's federal delegation, including senators, Joni Ernst and Chuck Grassley, and representative, Mariannette Miller-Meeks, introduced a resolution to recognize Clark for breaking the NCAA Division I scoring record.

[305] In February 2024, Clark became the top-selling college athlete on the online sports merchandise retailer Fanatics, surpassing Colorado Buffaloes quarterback, Shedeur Sanders.