Jefferson played point guard for UConn women's basketball team, where she won four consecutive national championships.

She finished her UConn career ranked first in assists, second in steals, and as a two-time winner of the Nancy Lieberman Award as the top point guard in the nation.

[1] Jefferson played five varsity seasons with the Texas Home Educators Sports Association (THESA) Riders as a homeschooled athlete.

Jefferson began playing with THESA's varsity squad as an eighth grader and compiled 509 points, 85 rebounds, and 87 assists.

Jefferson averaged 5.6 points per game, and, although the shortest player on the team at 5 ft 6 in (1.68 m), she tied for third in blocks with five over the course of the event.

Jefferson led UConn to a 151–5 record over her four-year career, which included four consecutive National Championships.

She finished her career in 22nd place on the UConn scoring list with 1,532, all-time leader in assists with 659, and second in steals with 353.

Jefferson was named the 2014–2015 American Athletic Conference and WBCA NCAA Division I Defensive Player of the Year, and Consensus first team All-American for the second straight season.

During her rookie season, Jefferson scored a game-winning putback to beat the buzzer as part of her career-high 31 points to help San Antonio defeat the Indiana Fever 87–85 in overtime on July 1, 2016.

In August 2016, Jefferson signed with Galatasaray of the Turkish Women's Basketball League (KBSL) for the 2016–17 season.

[16] In September 2016, Jefferson was featured in the Adidas "Sport Needs Creators" ad[17] alongside athletes including Von Miller of the Denver Broncos, Paul Pogba of Manchester United, and James Harden of the Houston Rockets.