Sabonis made his pro debut in 1981 with BC Žalgiris in his hometown, Kaunas. He won three consecutive Soviet League titles and reached the 1986 Euroleague finals with the team.

Sabonis was selected by the Atlanta Hawks with the 77th pick of the 1985 NBA Draft. However, the selection was voided because Sabonis was under 21 at the time of the draft. The following spring, he suffered a devastating Achilles' tendon injury. Nevertheless, he was selected by the Portland Trail Blazers with the 24th pick of the 1986 NBA Draft.

Sabonis wasn't allowed to play in the NBA by Soviet authorities until 1989. However, he did go to Portland to rehabilitate his injury with Blazers trainers. He also practiced with the team.

In the 1988 Summer Olympics, Sabonis led the Soviet Union to a gold medal win against a United States team that featured future NBA All-Stars David Robinson, Mitch Richmond and Danny Manning. The team later beat Yugoslavia in the finals.

In 1992, after playing with CB Valladolid for three seasons, Sabonis joined Real Madrid and won two Spanish League titles and a Euroleague title in 1995. During the 1994-95 regular season with Real Madrid, he averaged 22.8 points, 13.2 rebounds, 2.6 blocked shots, and 2.4 assists per game.

In 1995, Sabonis signed with the Blazers. He had a successful rookie campaign, averaging 14.5 points on 55% shooting and 8.1 rebounds. Sabonis was selected to the All-Rookie First Team and was runner-up in both Rookie of the Year and Sixth Man of the Year votings. His postseason averages were up to 23.6 points and 10.2 rebounds.

Sabonis averaged 16.0 points, 10.0 rebounds and 3.0 assists in 1997-98, all career-highs.

He won the European Player of the Year twice while playing with the Blazers. He also became a fan favorite.

The question that surrounds Sabonis' NBA career revolves around how good he could have been had he played in the NBA during his prime.Sabonis was over 31 when he joined the Blazers, by which time he had already won multiple gold medals and suffered through numerous injuries.

Sabonis came back to Žalgiris to play his final season. He led the team to the Top 16 stage of the season and was named the Regular Season MVP and the Top 16 MVP. He also became the team's president.