Viktor Fischer scored in each half to pave the way for a win that increased the gap on PSV Eindhoven after they could only draw 2-2 at relegation-threatened Roda JC.
Fischer opened the scoring on 21 minutes before a Rens Van Eijden own goal gave Ajax full control. Fischer's second on 77 minutes was quickly nullified by a Nick Van der Velden goal but substitute Ryan Babel scored nine minutes from the end to ensure a wide-margin win.
Ajax's success was made even more important when PSV Eindhoven conceded an 87th-minute Sanharib Malki equaliser at Roda JC.
Roda led through Frank Demouge on 14 minutes but PSV fired ahead before half-time thanks to an Ola Toivonen double. But Roda, who remain inside the relegation play-off places, snatched a point through Malki.
PSV's slip allowed Vitesse Arnhem to draw level in second place as they extended their winning run to six games with a 2-1 win over PEC Zwolle.
Wilfried Bony and Mike Havenaar fired them 2-0 by the break with Zwolle's sole reply coming via Arsenio Valpoort with 12 minutes left.
RKC Waalwijk thumped ADO Den Haag 4-0 to edge away from the relegation places.
Mart Lieder got the ball rolling on 10 minutes before a Vito Wormgoor own goal and Robert Braber's goal just before half-time all but settled the match. Henrico Drost completed the rout on 88 minutes.
AZ Alkmaar grabbed a much-needed win 2-1 at Heracles Almelo despite playing with 10 men for almost an hour.
Markus Henriksen's 22nd-minute opener was followed by a Mike te Wierik own goal two minutes later to give AZ a 2-0 lead.
Thomas Lam saw red on the hour but Heracles were only able to pull a single goal back when Te Wierik made up for his earlier blunder with a 43rd-minute goal.