Milton-Jones accepted an athletic scholarship to attend the University of Florida in Gainesville, Florida, where she played for coach Carol Ross's Florida Gators women's basketball team from 1993 to 1997. She was a four-year letterman, and led the Lady Gators to four consecutive NCAA Tournament appearances. As a senior in 1996–97, she was recognized as an All-American by the Associated Press, Kodak and the Basketball Times; she was also the winner of the Wade Trophy, recognizing the best women's basketball player in NCAA Division I.
Milton-Jones represented the USA at the 1997 World University Games held in Marsala, Sicily, Italy in August 1997. The USA team won all six games, earning the gold medal at the event. Milton-Jones averaged 10.3 points per game and recorded 14 steals, second highest on the team.
Milton-Jones was named to the U.S. national team in 1998. The national team traveled to Berlin, Germany in July and August 1998 for the FIBA World Championships. The U.S. team won a close opening game against Japan 95–89, then won their next six games easily. In the semifinal game against Brazil, the U.S. team was behind as much as ten points in the first half, but the U.S. team went on to win 93–79. The gold medal game was a rematch against Russia. In the first game, the Americans dominated almost from the beginning, but in the rematch, the Russian team took the early lead and led much of the way. With under two minutes remaining, the U.S. team was down by two points but the Americans responded, then held on to win the gold medal 71–65. Milton-Jones averaged 7.1 points per game.
In the WNBA, she played for the Los Angeles Sparks from 1999 to 2004. She was traded to the Washington Mystics in exchange for Chamique Holdsclaw and a first-round draft pick in the 2004 off-season. In 2003, she won the Euroleague Championship with team Ekaterinburg in Russia. In the 2005–06 season, she won the Euroleague with Gambrinus Brno of the Czech Republic and for the season 2006–07 she signed a two-year contract with Ros Casares Valencia of Spain. During the 2008–2009 WNBA off-season, Milton-Jones played for Ros Casares Valencia in Spain. for whom she also played during the 2007-08 off-season.
She is a two-time WNBA champion and has been selected to the WNBA All Star Game multiple times. In her WNBA career, she has scored 3,944 career points (16th all-time). On April 22, 2008, Milton-Jones was reacquired by the Los Angeles Sparks in a trade for Taj McWilliams-Franklin.