The Pacers, who have lost 11 in a row in San Antonio and gone 1-14 there since Duncan was drafted first overall in 1997, visit the Spurs in a meeting of two of the league's top teams.
Indiana (17-2) has been the best defensive squad in the NBA this season, allowing league lows in both points (87.5) and shooting percentage (39.5).
Anchored by center Roy Hibbert, who averages 3.4 blocks, the Pacers have the length and physicality to control the defensive end. Only three times this season has Indiana allowed 100 or more points - it lost two of those games - and the team is outrebounding opponents by a 4.1 margin.
On Wednesday, the Pacers limited Utah to 41.3-percent shooting while forcing 14 turnovers, which led to 20 points in a 95-86 win.
"We made those guys take tough shots and, over time, those shots start to get a little short or a little long," Pacers forward Paul George said. "Our defense played a huge part in us getting this win."
George has been the leader on the other end of the floor, averaging a team-high 24.6 points while also chipping in 5.9 rebounds and 3.4 assists. George scored a career-high 43 in Monday's 106-102 loss at Portland. That came on the heels of the small forward being named the Eastern Conference Player of the Month for November.
Both of the Pacers' losses have come on the road, but the team has played well against some of the NBA's top competition and is 2-1 on its current five-game trip.
They opened the swing with a victory over the Los Angeles Clippers and will now face two more of the West's best teams before returning home. The Pacers close the trip at Oklahoma City on Sunday.
"It's a great opportunity for our team to grow and compete against some of the better teams in the NBA," forward David West said of the next two contests.
Beating Duncan and the Spurs (15-3) won't be easy, especially at AT&T Center. Indiana's only victory there since 1997 was a 92-82 victory on Jan. 4, 2002.
San Antonio has been terrific in its building this season, going 8-1 and shooting 50.3 percent from the field.
At 37, Duncan is averaging a career-low 13.1 points while playing just 27.9 minutes per game, but he offered a vintage performance Monday against Atlanta. He hit the winning jumper in the final second and finished with 23 points and 21 rebounds in a 102-100 win over the Hawks.
Duncan became the oldest player with 20 or more points and 20 or more boards since the NBA began keeping track of rebounds during the 1985-86 season.
"I feel a lot healthier now," he said. "For a while there, I was dealing with some stuff, but now my body is feeling good and I'm starting to get my legs underneath me."
The Spurs were scheduled to play Wednesday night against the Timberwolves in Mexico City, but the game was postponed because of smokey conditions in the arena. It will be made up in Minnesota at a later date.