Santana, the Dodgers' No. 12 prospect, matched his career high with 11 strikeouts and threw 72 of his 100 pitches for strikes across seven scoreless innings.
The 21-year-old got off to a fast start, striking out five in a row across the first and second innings and retiring 10 of the first 11 batters faced.
Santana, who posted a 4.11 ERA in 24 games across two levels this season, walked two and yielded just three hits in the outing.
The win secured the Drillers a spot in the Texas League Finals, where they will take on the Midland RockHounds.
Other top prospect performances from Sunday's action:
• No. 55 overall prospect Fernando Tatis Jr. (Padres No. 4) provided all of Double-A San Antonio's offense with one swing as he hit a solo homer in a loss to Midland. Tatis, who finished 1-for-4, hit .350 in five games during the playoffs after batting .278 across two levels during the regular season.
• No. 93 overall prospect Tyler O'Neill (Cardinals' No. 4) hit his third homer of the postseason in Triple-A Memphis' 13-10 win over Colorado Springs in the decisive Game 5 of the Pacific Coast League semifinals. O'Neill, who came up big with a 3-for-6, four-RBI performance in Game 4, put the Redbirds on the board early with a two-run homer in the first before finishing 3-for-5 with three RBIs.
• Athletics No. 11 prospect Sean Murphy helped propel Double-A Midland to the Texas League finals with a solo homer in a win over San Antonio. Murphy, who hit a career-high 13 homers during the season, has gone deep twice in five games during the postseason.
• Brewers No. 19 prospect Jacob Nottingham came through off the bench with a clutch two-out hit for Triple-A Colorado Springs. Nottingham was called upon as a pinch-hitter and came up with an RBI single in the ninth inning, but it wasn't enough as the Sky Sox comeback bid ultimately fell short.
• D-backs' No. 24 prospect Andy Yerzy put up a pair of extra-base hits, but it wasn't enough as Rookie-level Missoula lost to Great Falls in Game 1 of the Pioneer League semifinals. Yerzy, who hit .298 with 13 homers during the regular season, hit a two-run homer in the sixth and later added a double, finishing 2-for-4 with two RBIs.
• Padres No. 27 prospect Reggie Lawson led Class A Fort Wayne to a win with five scoreless innings on the mound. Lawson, who posted a 5.30 ERA across 17 starts this season, gave up four hits and struck out five as the TinCaps evened up the Midwest League semifinals 1-1 with Dayton.
• Rays prospects Joe McCarthy (No. 18) and Nick Ciuffo (No. 25) combined to go 3-for-8 in Double-A Montgomery's loss to Pensacola. McCarthy led off the game with a solo homer, his second of the postseason, and Ciuffo finished 2-for-4 with an RBI of his own.
• Twins prospects Lewin Diaz (No. 10) and Travis Blankenhorn (No. 11) came up clutch for Class A Cedar Rapids in a much-needed win over Quad Cities. The duo combined to 3-for-7 with two RBIs as the Kernels tied up the Midwest League semifinals at one game apiece. Blankenhorn homered as part of a 1-for-3 game, while Diaz went 2-for-4 and scored a pair of runs.
• Twins No. 17 prospect LaMonte Wade had a productive day and helped lift Double-A Chattanooga to a share of the Southern League title as he went 3-for-4 at the plate. Wade led off the ninth with a base hit and scored the tying run on Jonathan Rodriguez's walk-off homer.