Gary Johnson's side looked like being frustrated when Harry Pell hit the post, but Rob Dickie's header and Dan Holman's 26th goal of the season secured all three points.
Pell was then sent off late on for a second bookable offence.
Guiseley's best effort came through James Hurst's deflected strike, which was easily saved by Jonathan Flatt.
With Forest Green only managing a draw at Braintree, Cheltenham need four points from their remaining three games to secure an immediate return to the Football League.
Guiseley meanwhile remain two points clear of the bottom four.
Cheltenham Town boss Gary Johnson told BBC Radio Gloucestershire:
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"It was a close game - Guiseley played very defensively and tried to catch us on the break and we weren't finding any holes really early on.
"I made a change because I felt we needed to do something different - give the lads some new people to break them down and it worked.
"Last ten minutes we got the two goals and sent our fans home happy and it's put us in a fantastic position now."
Cheltenham scored two late goals to beat Guiseley and move within touching distance of the National League title.