With the small matter of an FA Trophy final at Wembley on the horizon, Sulphurites chief Simon Weaver made eight changes to his starting line-up, but the hosts still had too much for their high-flying visitors on a wet night evening in North Yorkshire.
It took Town just nine minutes to get off the mark, Ryan Fallowfield getting forward from right-back and delivering a low cross which Kiernan met at the near post and guided past a helpless Callum Burton.
The home advantage was doubled four minutes later, Kiernan's back-heel freeing up Fallowfield, who once again sent a dangerous right-wing centre into the United six-yard-box where the waiting Mark Beck could hardly miss.
And Harrogate were in dreamland with 20 minutes on the clock after Greg Taylor's dreadful attempt at a header back to Burton sent Kiernan clean through on goal.
The livewire attacker touched the ball past the U's custodian, but was brought down inside the box as he attempted to race past him and calmly converted the resulting spot-kick himself.
Cambridge are however second in the table for a reason and got themselves back into the contest after 26 minutes when veteran midfielder Wes Hoolahan swept home a first-time finish from 16 yards out.
Soon afterwards, the deficit was reduced to just one goal as Luke Hannant was afforded time and space inside the home area to shoot beyond Joe Cracknell.
Town were back in control of the contest moments later though, Kiernan tapping in from barely a yard out after Burton made a mess of dealing with George Thomson's tame strike.
With nothing to lose and needing just a point to secure automatic promotion, the visitors came out and had a real go in the second period, reducing the deficit at 4-3 just before the hour-mark through the prolific Paul Mullin's close-range effort.
And the United comeback was completed on 74 minutes as Jay Williams was penalised for a lunge on Hoolahan and Mullin took his tally to the season for 31 from 12 yards.
At that stage, Cambridge looked the more likely of the sides to go on and win the game, though it was Kevin Lokko who side-footed home the night's decisive goal six minutes from time.
Victory lifts Harrogate up to 15th in the League Two standings with just one fixture left to play this season.
Harrogate Town: Cracknell; Fallowfield, Smith, Lokko, Roberts (Burrell 67); Thomson, Williams, Francis, Hondermarck; Kiernan, Beck. Unused substitutes: Belshaw, Falkingham, Muldoon, McPake, Andrews.
Cambridge United: Burton; Knoyle, Drysdale (Okedina 46), Taylor, Iredale (Dunk 46); Hannant, Digby (Tracey 89), Hoolahan, Boateng (May 83); Mullin, Ironside. Unused substitutes: McKenzie-Lyle, O'Neil, Alese.
Referee: O Yates (Staffordshire).