Adam Hlozek and Patrik Schick scored either side of half-time to give the league leaders a two-goal cushion, with Yannik Keitel claiming a consolation.
The victory kept Xabi Alonso’s side 10 points clear at the top of the table, with Freiburg in ninth.
Bayern Munich had closed the gap to seven points after beating rock-bottom Darmstadt 5-2 on Saturday, but Leverkusen showed no signs of pressure as they restored their healthy advantage.
Coming into this game, Freiburg and Leverkusen experienced contrasting emotions on Thursday in the last 16 of the Europa League.
West Ham ran out 5-0 winners against Freiburg to send them out of the competition, but Leverkusen reached the quarter-finals as two injury-time goals from Schick sealed a dramatic 5-4 aggregate victory against Qarabag.
Leverkusen started this game in the same fashion they ended that European encounter as Wirtz beautifully curled the ball into the far corner with just 85 seconds on the clock.
Doan threatened to spoil their day when he picked his spot perfectly after a neat one-two inside the box, but Freiburg created little else throughout the game.
Indecision at the back, which saw goalkeeper Noah Atubolu lose the ball, handed Hlozek the chance to roll into an open net to give Leverkusen a half-time lead.
Schick then met Jeremie Frimpong’s cross with a deft touch to give Leverkusen breathing space in the 53rd minute, before substitute Keitel pulled one back for Freiburg 26 minutes later.
Leverkusen are yet to lose a game across all competitions in 2023-24 and have just eight games left to play in the Bundesliga as they look to claim their first-ever league title.