Two goals in the opening 12 minutes secured Mansfield a third straight win - and condemned Eastbourne to a fourth successive defeat.
Gary Mills set up Kyle Perry to put the Stags in front from close range.
Rob Duffy then doubled their advantage with a low shot into the bottom left corner for his ninth of the season.
Substitute Liam Enver-Marum pulled one back with a speculative effort that looped over visiting keeper Alan Marriott, but Mansfield held on.
Eastbourne manager Garry Wilson told BBC Sussex:
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"We came here today and we asked our players to compete and I thought we competed really well.
"Obviously my disappointment was with the two goals we conceded early on, take them out the game and I'm pleased with my team's performance."
Eastbourne Borough: Jordan, Baker (Elphick 46), Jenkins, Austin, Pullan, Smith, Armstrong, Atkin, Matt Crabb, Taylor (Enver-Marum 64), Brown. Subs Not Used: Knowles, Smart, Johnson.
Booked: Austin.
Goals: Enver-Marum 68.
Mansfield: Marriott, Heckingbottom, Mills, Jones, Garner, Somner, Duffy, Istead (Williams 80), Silk, Speight, Perry (Dobson 75). Subs Not Used: Eley, Armstrong, Sturrock.
Booked: Speight, Duffy.
Goals: Perry 6, Duffy 12.
Att: 1,207.
Ref: M Thompson (England).
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