Despite being in the relegation zone and facing the team who are second, the Lions took the lead due to an own goal when Sam Habergham tried to clear a low cross from the left but sliced it powerfully into his own net.
Lincoln were only able to create one chance during the opening 45 minutes when Theo Robinson fired straight at Guiseley keeper Jonny Maxted from inside the box.
Lincoln levelled at the start of the second half when Ash Palmer was adjudged to have fouled Adam Marriott in the area and Alan Power converted the spot-kick.
Adam Boyes was sent off for two yellows and Lincoln took advantage, scoring from a late corner from Sean Raggett.
Captain Danny Lowe became their second man to see red and Nathan Arnold wrapped up the win.
Lincoln City: Farman, Wood, Habergham, Hawkridge, Power (Muldoon 85), Waterfall, Rhead (Howe 90), Raggett, Arnold, Woodyard, Robinson (Marriott 55). Unused substitutes: Miles, Walton.
Guiseley: Maxted, Brown, Lowe, Preston (Purver 90), Boyes, Hatfield, Palmer, Williams, Walton (Green 90), Cassidy, Wesolowski. Unused substitutes: Johnson, Atkinson, Logan.
Referee: Chris O’Donnell.